Which individual, social, and urban factors in early childhood predict psychopathology in later childhood, adolescence and young adulthood? A systematic review.

Background: A comprehensive picture is lacking of the impact of early childhood (age 0-5) risk factors on the subsequent development of mental health symptoms. Objective: In this systematic review, we investigated which individual, social and urban factors, experienced in early childhood, contribute to the development of later anxiety and depression, behavioural problems, and internalising and externalising symptoms in youth. Methods: Embase, MEDLINE, Scopus, and PsycInfo were searched on the 5th of January 2022. Three additional databases were retrieved from a mega-systematic review source that focused on the identification of both risk and protective indicators for the onset and maintenance of prospective depressive, anxiety and substance use disorders. A total of 46,450 records were identified and screened in ASReview, an AI-aided systematic review tool. We included studies with experimental, quasi-experimental, prospective and longitudinal study designs, while studies that focused on biological and genetical factors, were excluded. Results: Twenty studies were included. The majority of studies explored individual-level risk factors (N = 16). Eleven studies also explored social risk factors and three studied urban risk factors. We found evidence for early predictors relating to later psychopathology measures (i.e., anxiety and depression, behavioural problems, and internalising and externalising symptoms) in childhood, adolescence and early adulthood. These were: parental psychopathology, exposure to parental physical and verbal violence and social and neighbourhood disadvantage. Conclusions: Very young children are exposed to a complex mix of risk factors, which operate at different levels and influence children at different time points. The urban environment appears to have an effect on psychopathology but it is understudied compared to individual-level factors. Moreover, we need more research exploring the interaction between individual, social and urban factors.

Treatments for partial remission of major depressive disorder: a systematic review and meta-analysis.

QUESTION: Partial remission of major depressive disorder (MDD) is a debilitating and distressing clinical state related to chronicity, morbidity and relapse. Although one-third of patients remit partially, evidence for treatment efficacy is unclear. We provide an overview of treatment options and their efficacy. STUDY SELECTION AND ANALYSIS: Embase, PsycINFO, Medline and SCOPUS were systematically searched through February 2023. Included were randomised controlled trials (RCTs) examining any treatment in patients with partially remitted MDD aged 13-65 years, reporting data on severity, remission or relapse. FINDINGS: Seven RCTs examining psychotherapy including 1024 patients were eligible. There were not enough RCTs to examine effects of pharmacotherapy. Psychotherapy was associated with lower depressive symptom severity at post-treatment (Hedges' g=0.50; 95% CI 0.23 to 0.76), but not at follow-up up to 1 year (Hedges' g=0.36; 95% CI -0.30 to 1.02) or longer (Hedges' g=0.02; 95% CI -0.09 to 0.12). Psychotherapy was associated with superior remission rates at post-treatment (OR 2.57; 95% CI 1.71 to 3.87) and follow-up 6 months or longer (OR 1.75; 95% CI 1.21 to 2.53), although not with improved relapse rates at post-treatment (OR 0.17; 95% CI 0.01 to 4.83) or follow-up 6 months or longer (OR 0.46; 95% CI 0.21 to 1.03). Overall methodological quality was poor. CONCLUSIONS: Psychotherapy targeting partial remission may be effective in lowering depressive symptom severity and patients may potentially achieve full remission twice as likely. Yet, long-term and prophylactic effects are lacking. Given the risk of chronicity, more high-quality RCTs are needed. PROSPERO REGISTRATION NUMBER: CRD42020188451.

Meta-Analysis: Relapse Prevention Strategies for Depression and Anxiety in Remitted Adolescents and Young Adults.

OBJECTIVE: Depression and anxiety cause a high burden of disease and have high relapse rates (39%-72%). This meta-analysis systematically examined effectiveness of relapse prevention strategies on risk of and time to relapse in youth who remitted. METHOD: PubMed, PsycInfo, Embase, Cochrane, and ERIC databases were searched up to June 15, 2021. Eligible studies compared relapse prevention strategies to control conditions among youth (mean age 13-25 years) who were previously depressed or anxious or with ≥30% improvement in symptoms. Two reviewers independently assessed titles, abstracts, and full texts; extracted study data; and assessed risk of bias and overall strength of evidence. Random-effects models were used to pool results, and mixed-effects models were used for subgroup analyses. Main outcome was relapse rate at last follow-up (PROSPERO ID: CRD42020149326). RESULTS: Of 10 randomized controlled trials (RCTs) that examined depression, 9 were eligible for analysis: 4 included psychological interventions (n = 370), 3 included antidepressants (n = 80), and 2 included combinations (n = 132). No RCTs for anxiety were identified. Over 6 to 75 months, relapse was half as likely following psychological treatment compared with care as usual conditions (k = 6; odds ratio 0.56, 95% CI 0.31 to 1.00). Sensitivity analyses including only studies with ≥50 participants (k = 3), showed similar results. Over 6 to 12 months, relapse was less likely in youth receiving antidepressants compared with youth receiving pill placebo (k = 3; OR 0.29, 95% CI 0.10 to 0.82). Quality of studies was suboptimal. CONCLUSION: Relapse prevention strategies for youth depression reduce risk of relapse, although adequately powered, high-quality RCTs are needed. This finding, together with the lack of RCTs on anxiety, underscores the need to examine relapse prevention in youth facing these common mental health conditions.

Psychotherapy for co-occurring symptoms of depression, anxiety and obsessive-compulsive disorder in children and adults with autism spectrum disorder: a systematic review and meta-analysis.

Individuals with autism spectrum disorder (ASD) struggle accessing psychotherapy services for comorbidities, including anxiety-, depressive- and obsessive-compulsive disorders (OCD). Apart from cognitive behavioural therapy (CBT) for anxiety in children with ASD, it is unclear whether psychotherapy is effective for these comorbid disorders.We therefore systematically reviewed any form of psychotherapy for co-occurring symptoms of anxiety, depression and OCD in individuals with ASD.Database searches were conducted until February 2022 using EMBASE, PsycINFO and PubMed. Randomised controlled trials (RCT) were included investigating any form of psychotherapy for symptoms of anxiety, depression and OCD in individuals with ASD. Summary data were extracted, and random-effects meta-analyses were conducted.For CBT 26 RCTs (n = 1251), and for social skills training (SST) 11 RCTs (n = 475) met criteria for inclusion. Pooled effect sizes indicated a moderate reduction of anxiety in children (g = -0.70) and a small reduction of depressive symptoms in adults (g = -0.39). For SST overall effect sizes were small for reduction of anxiety in children (g = -0.35) and adults (g = -0.34) and moderate for reduction of depressive symptoms in children (g = -0.50). Risk of bias was high in 18, moderate in 16 and low in 3 RCTs.Our results provide new and age-specific evidence that: (1) CBT is effective for reducing anxiety in children and to a lesser extent for depressive symptoms in adults with ASD; and (2) social skills interventions are effective for reducing anxiety in children and adults and for depressive symptoms in children with ASD.

Are neuromodulation interventions associated with changes in the gut microbiota? A systematic review.

The microbiota-gut-brain axis (MGBA) refers to the bidirectional communication between the brain and the gut microbiota and recent studies have linked the MGBA to health and disease. Research has so far investigated this axis mainly from microbiota to brain but less is known about the other direction. One approach to examine the MGBA from brain to microbiota is through understanding if and how neuromodulation might impact microbiota. Neuromodulation encompasses a wide range of stimulation techniques and is used to treat neurological, psychiatric and metabolic disorders, like Parkinson's Disease, depression and obesity. Here, we performed a systematic review to investigate whether neuromodulation is associated with subsequent changes in the gut microbiota. Searches in PsycINFO and MEDLINE were performed up to March 2022. Included studies needed to be clinical or preclinical studies comparing the effects of deep brain stimulation, electroconvulsive therapy, repetitive transcranial magnetic stimulation, transcranial direct current stimulation or vagal nerve stimulation on the gut microbiota before and after treatment or between active and control groups. Seven studies were identified. Neuromodulation was associated with changes in relative bacterial abundances, but not with (changes in) α-diversity or ß-diversity. Summarizing, currently reported findings suggest that neuromodulation interventions are associated with moderate changes in the gut microbiome. However, findings remain inconclusive due to the limited number and varying quality of included studies, as well as the large heterogeneity between studies. More research is required to more conclusively establish whether, and if so, via which mechanism(s) of action neuromodulation interventions might influence the gut microbiota.

Tapering Antidepressants While Receiving Digital Preventive Cognitive Therapy During Pregnancy: An Experience Sampling Methodology Trial.

Background: Previous studies indicated that affect fluctuations, the use of antidepressant medication (ADM), as well as depression during pregnancy might have adverse effects on offspring outcomes. The aim of the current proof-of-principle study is to explore the effect of tapering ADM while receiving online preventive cognitive therapy (PCT) on pregnant women and the offspring as compared to pregnant women continuing ADM. Objectives: We sought to compare positive and negative affect fluctuations in pregnant women receiving online PCT while tapering ADM vs. pregnant women continuing ADM, and to investigate if affect fluctuations in early pregnancy were related to offspring birth weight. Method: An experience sampling methodology (ESM)-trial ran alongside a Dutch randomized controlled trial (RCT) and prospective observational cohort of women using ADM at the start of pregnancy. In the ESM-trial fluctuations of positive and negative affect were assessed in the first 8 weeks after inclusion. Recurrences of depression were assessed up to 12 weeks post-partum, and birth records were used to assess offspring birth weight. The RCT has been registered at the Netherlands Trial Register (NTR4694, https://www.trialregister.nl/trial/4551). Results: In total, 19 pregnant women using ADM at start of their pregnancy participated in the ESM-trial. There were no significant differences in positive and negative affect fluctuations, nor recurrence rates between women receiving PCT while tapering ADM vs. women continuing ADM. We found no association between affect fluctuations, pre-natal depressive symptoms, and birth weight (all p > 0.05). Conclusion: This explorative study showed that tapering ADM while receiving online PCT may protect pregnant women against recurrences of depression and affect fluctuations, without affecting birth weight. There is a high need for more controlled studies focusing on tapering ADM with (online) psychological interventions during pregnancy.

Dose-effect of maternal serotonin reuptake inhibitor use during pregnancy on birth outcomes: A prospective cohort study.

BACKGROUND: While antidepressant use during pregnancy is increasingly common, there is concern about the possible effects of in-utero antidepressant exposure on the child. Our objective was to examine whether there is a dose-effect of maternal serotonin reuptake inhibitors (SRI) during pregnancy on birth outcomes. METHODS: Women between 12 and 16 weeks of gestation, who were using an SRI, were eligible for participation in this nation-wide prospective observational cohort study. Recruitment took place between April 2015 and February 2018 (n = 145). SRI exposure and psychopathology symptoms were assessed throughout pregnancy. Exposure was defined as SRI standardized dose at 36 weeks of gestation and mean SRI standardized dose over total pregnancy. Multivariable linear and logistic regression were used to examine the associations with birth weight, gestational age at birth, and being small for gestational age. RESULTS: Maternal SRI dose at 36 weeks of gestation was significantly associated with birth weight (adjusted ß = -180.7, 95%CI -301.1;-60.2, p-value < 0.01) as was mean SRI standardized dose during total pregnancy (adjusted ß = -187.3, 95%CI -322.0;-52.6, p-value < 0.01). No significant associations between maternal SRI dose and gestational age or being small for gestational age were observed. LIMITATIONS: Although prospective, we cannot make full causal inferences given that we did not randomize women to different dosages. CONCLUSION: These findings suggest that careful dosing of SRI use during pregnancy may prevent a negative impact on birth weight and indicate the need for further investigation of causality.

Individual participant data (IPD) meta-analysis of psychological relapse prevention interventions versus control for patients in remission from depression: a protocol.

INTRODUCTION: Psychological interventions and antidepressant medication can be effective interventions to prevent depressive relapse for patients currently in remission of depression. Less is known about overall factors that predict or moderate treatment response for patients receiving a psychological intervention for recurrent depression. This is a protocol for an individual participant data (IPD) meta-analysis which aims to assess predictors and moderators of relapse or recurrence for patients currently in remission from depression. METHODS AND ANALYSIS: Searches of PubMed, PsycINFO, Embase and Cochrane Central Register of Controlled Trials were completed on 13 October 2019. Study extractions and risk of bias assessments have been completed. Study authors will be asked to contribute IPD. Standard aggregate meta-analysis and IPD analysis will be conducted, and the outcomes will be compared with assess whether results differ between studies supplying data and those that did not. IPD files of individual data will be merged and variables homogenised where possible for consistency. IPD will be analysed via Cox regression and one and two-stage analyses will be conducted. ETHICS AND DISSEMINATION: The results will be published in peer review journals and shared in a policy briefing as well as accessible formats and shared with a range of stakeholders. The results will inform patients and clinicians and researchers about our current understanding of more personalised ways to prevent a depressive relapse. No local ethics approval was necessary following consultation with the legal department. Guidance on patient data storage and management will be adhered to. PROSPERO REGISTRATION NUMBER: CRD42019127844.

Psychological theories of depressive relapse and recurrence: A systematic review and meta-analysis of prospective studies.

Psychological factors hypothesized to account for relapse of major depressive disorder (MDD) roughly originate from five main theories: Cognitive, diathesis-stress, behavioural, psychodynamic, and personality-based. In a meta-analysis we investigated prospective, longitudinal evidence for these leading psychological theories and their factors in relation to depressive relapse. Included studies needed to establish history of MDD and prospective depressive relapse through a clinical interview, have a longitudinal and prospective design, and measure at least one theory-derived factor before relapse. We identified 66 eligible articles out of 43,586 records published up to November 2018. Pooled odds ratios (OR) indicated a significant relationship between the cognitive, behavioural, and personality-based theories and depressive relapse (cognitive: k = 17, OR = 1.24, 95% CI = 1.10-1.40; behavioural, k = 8, OR = 1.15, 95% CI = 1.05-1.25; personality: k = 12, OR = 1.26, 95% CI = 1.02-1.54), but not for the psychodynamic theories (k = 4, OR = 1.29, 95% CI = 0.83-1.99). Pooled hazard ratios of the theories were not significant. There were no articles identified for the diathesis-stress theories. To conclude, there is a restricted number of prospective studies, and some evidence that the cognitive, behavioural, and personality-based theories indeed partially account for depressive relapse.

Recurrence of depression in the perinatal period: Clinical features and associated vulnerability markers in an observational cohort.

OBJECTIVE: Antidepressant medication is commonly used for the prevention of depression recurrence in the perinatal period, yet it is unknown what vulnerability markers may play a role in recurrence. The objective of the current study was to provide a descriptive overview of the associated characteristics of women who experienced a perinatal recurrence of depression despite ongoing antidepressant use, and further, to identify clinically measurable vulnerability markers associated with recurrence. METHODS: Eighty-five pregnant women with a history of depression who used antidepressants (e.g. Selective Serotonin Reuptake Inhibitors or Serotonin and Noradrenaline Reuptake Inhibitors) at the start of the study were included. Clinical features, including information on psychiatric history and antidepressant use, were collected throughout the perinatal period (in this study defined as the period between 12 weeks of pregnancy untill three months postpartum). The clinical features of women experiencing recurrence of depression were described in detail. To identify vulnerability markers associated with recurrence of depression, we performed exploratory univariable logistic regression analyses. RESULTS: Eight women (9.4%) experienced a recurrence of depression; two during pregnancy and six in the first 12 weeks postpartum. All women with recurrence of depression had first onset of depression during childhood or adolescence and had at least 2 psychiatric co-morbidities. Identification of vulnerability markers associated with recurrence of depression yielded associations with depressive symptoms around 16 weeks of pregnancy (OR 1.28, 95%CI 1.08-1.52), number of psychiatric co-morbidities (OR 1.89, 95%CI 1.16-3.09) and duration of antidepressant use (OR 1.01, 95%CI 1.00-1.02). CONCLUSION: Implementing adequate risk assessment in pregnant women who use antidepressants can help identify predictors for recurrence of depression in future studies and thus ultimately lead to improved care.

Dysfunctional attitudes or extreme response style as predictors of depressive relapse and recurrence after mobile cognitive therapy for recurrent depression.

BACKGROUND: According to previous research, dysfunctional attitudes and/or scoring extreme on the end-point anchors of questionnaires of dysfunctional thinking predict depressive relapse/recurrence. Evidence that these two methods represent a risk for depressive relapse/recurrence is however mixed, due to differential or poorly defined concepts. The current study aimed to test the two methods. METHODS: Remitted recurrently depressed patients with low residual depressive symptoms (N = 264) were recruited as part of a randomized controlled trial of the effectiveness of mobile Cognitive Therapy for recurrent depression versus treatment as usual. In the current secondary analysis, Cox regression models were conducted to test dysfunctional attitudes and extreme responding variables (assessed on the Dysfunctional Attitudes Scale [DAS]) as predictors of depressive relapse/recurrence within two years after randomization. RESULTS: Data from 255 participants were analyzed. Results showed that DAS total scores at baseline significantly predicted depressive relapse/recurrence (Hazard Ratio [HR] = 1.01, p = .042). An index that reflects endorsement of habitual relative to functional responses was a significant predictor of depressive relapse/recurrence (HR = 2.11, p = .029). LIMITATIONS: The current study employed a single measure to identify extreme responses and dysfunctional attitudes. Secondly, various statistical analyses were performed without correcting for multiple testing, which in turn increased the likelihood to finding significant results. CONCLUSIONS: Current study confirmed both methods: People who scored higher on the DAS or had relatively more habitual than functional responses on the extreme positive ends of the DAS had a decreased time to depressive relapse/recurrence.

Offspring outcomes after prenatal interventions for common mental disorders: a meta-analysis.

BACKGROUND: It is presumed that pharmacological and non-pharmacological treatment of prenatal common mental disorders can mitigate associated adverse effects in offspring, yet strong evidence for the prophylactic benefits of treatment is lacking. We therefore examined the effect of prenatal treatments for common mental disorders on offspring outcomes. METHODS: For this meta-analysis, articles published up to August 31, 2017, were obtained from PubMed, PsycInfo, Embase, and Cochrane databases. Included studies needed to be randomized controlled trials (RCTs) on the effect of treatment of prenatal common mental disorders comparing an intervention to a control condition, including offspring outcome(s). Random effects models were used to calculate Hedges' g in the program Comprehensive Meta-Analysis© (version 3.0). RESULTS: Sixteen randomized controlled trials among 2778 pregnant women compared offspring outcomes between prenatal interventions and control groups. There were zero pharmacological, 13 psychological, and three other interventions (homeopathy, relaxation interventions, and short psycho-education). Birth weight (mean difference 42.88 g, g = 0.08, 95% CI -0.06 to 0.22, p = 0.27, n = 11), Apgar scores (g = 0.13, 95% CI -0.28 to 0.54, p = 0.53, n = 4), and gestational age (g = 0.03, 95% CI -0.06 to 0.54, p = 0.49, n = 10) were not significantly affected. Other offspring outcomes could not be meta-analyzed due to the inconsistent reporting of offspring outcomes and an insufficient number of studies. CONCLUSIONS: Non-pharmacological interventions had no significant effect on birth outcomes, although this outcome should be considered with caution due to the risk of biases. No randomized controlled trial examined the effects of prenatal pharmacological treatments as compared to treatment as usual for common mental disorders on offspring outcomes. Present clinical guidelines may require more research evidence on offspring outcomes, including child development, in order to warrant the current recommendation to routinely screen and subsequently treat prenatal common mental disorders. TRIAL REGISTRATION: PROSPERO CRD42016047190.

Antidepressants during pregnancy: Guideline adherence and current practice amongst Dutch gynaecologists and midwives.

BACKGROUND AND OBJECTIVES: prescription rates of antidepressants during pregnancy range from 2-3% in The Netherlands to 6.2% in the USA. Inconclusive evidence about harms and benefits of antidepressants during pregnancy leads to variation in advice given by gynaecologists and midwives. The objective was to investigate familiarity with, and adherence to the Dutch multidisciplinary guideline on Selective Serotonin Reuptake Inhibitor (SSRI) use during pregnancy by gynaecologists and midwives in the Netherlands. METHODS: an online survey was developed and send to Dutch gynaecologists and midwives. The survey consisted mainly of multiple-choice questions addressing guideline familiarity and current practice of the respondent. Also, caregiver characteristics associated with guideline adherence were investigated. FINDINGS: a total of 178 gynaecologists and 139 midwives responded. Overall familiarity with the Dutch guideline was 92.7%. However, current practice and advice given to patients by caregivers differed substantially, both between gynaecologists and midwives as well as within both professions. Overall guideline adherence was 13.9%. Multivariable logistic regression showed that solely caregiver profession was associated with guideline adherence, with gynaecologists having a higher adherence rate (OR 2.10, 95%CI 1.02-4.33) than midwives. KEY CONCLUSION: although reported familiarity with the guideline is high, adherence to the guideline is low, possibly resulting in advice to patients that is inconsistent with guidelines and unwanted variation in current practice. IMPLICATIONS FOR PRACTICE: further implementation of the recommendations as given in the guideline should be stimulated. Additional research is needed to examine how gynaecologists and midwives can be facilitated to follow the recommendations of the clinical guideline on SSRI use during pregnancy.

Myocardial Injury in Patients With Sepsis and Its Association With Long-Term Outcome.

BACKGROUND: Sepsis is frequently complicated by the release of cardiac troponin, but the clinical significance of this myocardial injury remains unclear. We studied the associations between troponin release during sepsis and 1-year outcomes. METHODS AND RESULTS: We enrolled consecutive patients with sepsis in 2 Dutch intensive care units between 2011 and 2013. Subjects with a clinically apparent cause of troponin release were excluded. High-sensitivity cardiac troponin I (hs-cTnI) concentration in plasma was measured daily during the first 4 intensive care unit days, and multivariable Cox regression analysis was used to model its association with 1-year mortality while adjusting for confounding. In addition, we studied cardiovascular morbidity occurring during the first year after hospital discharge. Among 1258 patients presenting with sepsis, 1124 (89%) were eligible for study inclusion. Hs-cTnI concentrations were elevated in 673 (60%) subjects on day 1, and 755 (67%) ever had elevated levels in the first 4 days. Cox regression analysis revealed that high hs-cTnI concentrations were associated with increased death rates during the first 14 days (adjusted hazard ratio, 1.72; 95% confidence interval, 1.14-2.59 and hazard ratio, 1.70; 95% confidence interval, 1.10-2.62 for hs-cTnI concentrations of 100-500 and >500 ng/L, respectively) but not thereafter. Furthermore, elevated hs-cTnI levels were associated with the development of cardiovascular disease among 200 hospital survivors who were analyzed for this end point (adjusted subdistribution hazard ratio, 1.25; 95% confidence interval, 1.04-1.50). CONCLUSIONS: Myocardial injury occurs in the majority of patients with sepsis and is independently associated with early-but not late-mortality, as well as postdischarge cardiovascular morbidity.

A masked negative self-esteem? Implicit and explicit self-esteem in patients with Narcissistic Personality Disorder.

The mask model of narcissism states that the narcissistic traits of patients with NPD are the result of a compensatory reaction to underlying ego fragility. This model assumes that high explicit self-esteem masks low implicit self-esteem. However, research on narcissism has predominantly focused on non-clinical participants and data derived from patients diagnosed with Narcissistic Personality Disorder (NPD) remain scarce. Therefore, the goal of the present study was to test the mask model hypothesis of narcissism among patients with NPD. Male patients with NPD were compared to patients with other PD's and healthy participants on implicit and explicit self-esteem. NPD patients did not differ in levels of explicit and implicit self-esteem compared to both the psychiatric and the healthy control group. Overall, the current study found no evidence in support of the mask model of narcissism among a clinical group. This implicates that it might not be relevant for clinicians to focus treatment of NPD on an underlying negative self-esteem.

Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: study protocol of a pragmatic multicentre non-inferiority randomized controlled trial.

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/DESIGN: '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. DISCUSSION: 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. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR4694 ; registration date: 16-jul-2014.