title: Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: study protocol of a pragmatic multicentre non-inferiority randomized controlled trial.
abstract: BACKGROUND
  Approximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still controversial. On the one hand SSRIs may be toxic to the intrauterine developing child, while on the other hand relapse or recurrence of depression during pregnancy poses risks for both mother and child. Among patients and professionals there is an urgent need for evidence from randomized studies to make rational decisions regarding continuation or tapering of SSRIs during pregnancy. At present, no such studies exist.
  
  
  METHODS
  'Stop or Go' is a pragmatic multicentre randomized non-inferiority trial among 200 pregnant women with a gestational age of less than 16 weeks who use SSRIs without clinically relevant depressive symptoms. Women allocated to the intervention group will receive preventive cognitive therapy with gradual, guided discontinuation of SSRIs under medical management (STOP). Women in the control group will continue the use of SSRIs (GO). Primary outcome will be the (cumulative) incidence of relapse or recurrence of maternal depressive disorder (as assessed by the Structured Clinical Interview for DSM disorders) during pregnancy and up to three months postpartum. Secondary outcomes will be child outcome (neonatal outcomes and psychomotor and behavioural outcomes up to 24 months postpartum), and health-care costs. Total study duration for participants will be therefore be 30 months. We specified a non-inferiority margin of 15 % difference in relapse risk.
  
  
  CONCLUSIONS
  This study is the first to investigate the effect of guided tapering of SSRIs with preventive cognitive therapy from early pregnancy onwards as compared to continuation of SSRIs during pregnancy. We will study the effects on both mother and child with a pragmatic approach. Additionally, the study examines cost effectiveness. If non-inferiority of preventive cognitive therapy with guided tapering of SSRIs compared to intended continuation of SSRIs is demonstrated for the primary outcome, this may be the preferential strategy during pregnancy.
  
  
  BACKGROUND
  Netherlands Trial Register (NTR): NTR4694 ; registration date: 16-jul-2014.
authors.affiliation: Department of Psychiatry, Erasmus Medical Centre, 's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Nina M
authors.initials: NM
authors.lastname: Molenaar
authors.affiliation: Department of Clinical Psychology, Utrecht University, Heidelberglaan 1, 3584 CS, Utrecht, The Netherlands.
authors.forename: Marlies E
authors.initials: ME
authors.lastname: Brouwer
authors.affiliation: Department of Clinical Psychology, Utrecht University, Heidelberglaan 1, 3584 CS, Utrecht, The Netherlands.
authors.forename: Claudi L H
authors.initials: CL
authors.lastname: Bockting
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus Medical Centre, 's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Gouke J
authors.initials: GJ
authors.lastname: Bonsel
authors.affiliation: Department of Pediatrics, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Christine N
authors.initials: CN
authors.lastname: van der Veere
authors.affiliation: Department of obstetrics and birth care, Hogeschool Rotterdam, Rochussenstraat 198, 3015 EK, Rotterdam, The Netherlands.
authors.forename: Hanneke W
authors.initials: HW
authors.lastname: Torij
authors.affiliation: Department of Psychiatry, Erasmus Medical Centre, 's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Witte J G
authors.initials: WJ
authors.lastname: Hoogendijk
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus Medical Centre, 's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Duvekot
authors.affiliation: Department of General Practice, University Medical Centre Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
authors.forename: Huibert
authors.initials: H
authors.lastname: Burger
authors.affiliation: Department of Psychiatry, Erasmus Medical Centre, 's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. mijke.vandenberg@erasmusmc.nl.|Department of Obstetrics and Gynaecology, Erasmus Medical Centre, 's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. mijke.vandenberg@erasmusmc.nl.|Department of Child and Adolescent Psychiatry, Erasmus Medical Centre - Sophia Childrens Hospital, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. mijke.vandenberg@erasmusmc.nl.
authors.forename: Mijke P
authors.initials: MP
authors.lastname: Lambregtse-van den Berg
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D011247:Pregnancy; D000928:Antidepressive Agents / Q000627:therapeutic use; D002985:Clinical Protocols; D015928:Cognitive Behavioral Therapy / Q000379:methods; D003866:Depressive Disorder / Q000188:drug therapy / Q000628:therapy; D009426:Netherlands; D011297:Prenatal Exposure Delayed Effects / Q000517:prevention & control; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D000074099:Equivalence Trials as Topic
chemical_list: D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Antidepressants; Cognitive therapy; Cost-effectiveness; Depression; Perinatal outcome; Pregnancy; Prevention; Recurrence; Relapse; SSRI; Selective serotonin reuptake inhibitors