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BACKGROUND: Women with bipolar I disorder are at high risk for severe episodes after childbirth, but there is no study that provides an overview on bipolar episode risk both during pregnancy and after childbirth, miscarriage and induced abortion. The aim of this study was to determine the episode risk during all pregnancy outcomes subdivided by first and subsequent pregnancies. METHODS: Participants were 436 women with bipolar I disorder from the Dutch Bipolar Cohort, having 919 pregnancies of which 762 resulted in a live childbirth, 118 ended in a miscarriage and 39 ended in induced abortion. Women reported on the occurrence of manic or depressed episodes during the perinatal period. Information about medication use was obtained by questionnaires. RESULTS: Episode risk was 5.2% during pregnancy, and 30.1% in the postpartum period, with a peak in the early postpartum period. Risk of an episode was highest after live birth (34.4%), and lower after miscarriage (15.2%) and induced abortion (27.8%). Women with an episode during pregnancy or postpartum were less likely to have a second child compared to women with an uneventful first pregnancy (cOR=0.34; 95%CI: 0.22-0.51; p

Objective: The primary indication for electroconvulsive therapy is medication-resistant major depression. There is some evidence that combining electroconvulsive therapy with an antidepressant, instead of electroconvulsive therapy monotherapy, might improve remission rates. However, data on this topic have not been systematically studied. We undertook a systematic review and meta-analysis to determine the effectiveness of an adjuvant antidepressant during electroconvulsive therapy for major depression. Methods: Embase, Medline Ovid, Web of Science, Cochrane Central, PsychINFO Ovid and Google Scholar were searched up to January 2019. Randomized controlled trials and cohort studies reporting on the influence of an adjuvant antidepressant on the efficacy of electroconvulsive therapy for major depression were included. Authors independently screened records, extracted data and assessed study quality. We reported this systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Nine studies were included in the meta-analysis. The meta-analysis revealed a significant advantage of adjuvant antidepressants versus placebo. The overall effect size per category of antidepressant was as follows: tricyclic antidepressants: Hedges’ g 0.32 (95% confidence interval: [0.14, 0.51]) ( k = 6) with low heterogeneity ( I2: 4%, p = 0.39); selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitors: Hedges’ g 0.27 (95% confidence interval: [0.03, 0.52]) ( k = 2) with a lack of heterogeneity ( I2: 0%, p = 0.89); and monoamine oxidase inhibitors: Hedges’ g 0.35 (95% confidence interval: [−0.07, 0.77]) with moderate heterogeneity ( I2: 43%, p = 0.17) ( k = 3). Conclusion: An adjuvant antidepressant enhances the efficacy of electroconvulsive therapy for major depression. Tricyclic antidepressants, selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitors and monoamine oxidase inhibitors showed the same effect size. However, the effect sizes of tricyclic antidepressants and monoamine oxidase inhibitors are most likely underestimated, due to insufficient doses in most of the included studies. We recommend the routine use of an adequately dosed antidepressant during electroconvulsive therapy for major depression.

Antidepressant use during pregnancy has increased over the last decades, while safety has been under debate. Our aim was to measure the international prevalence of antidepressant use before, during, and after pregnancy and examine timing, type of prescriptions and geographic variability.We searched Embase, Medline Ovid, Web of Science, Cochrane Central and Google Scholar from their inception until February 19, 2019. We determined pooled prevalence estimates of antidepressants before, during, and after pregnancy, as well as stratified according to substantive variables.We identified 40 cohorts from 15 countries, together reporting on 14,072,251 pregnancies. Included studies had a low risk of bias, often reporting on large representative cohorts. Selective serotonin reuptake inhibitors (SSRIs) were the most commonly used antidepressants during pregnancy, with an international prevalence estimate of 3.0% (95%CI 2.3;3.7). While Europe and Australasia had pooled prevalence estimates of 1.6% and 1.3% respectively, Northern America had a prevalence estimate of 5.5% (Q-value = 126.19; df = 2; p-value0.01). Highest SSRI prevalence rates were found for sertraline (1.10%), followed by citalopram and fluoxetine (0.77% and 0.76% respectively) (Q-value = 121.25; df = 5; p-value0.01). Qualitative analysis indicated an increase in antidepressant use over subsequent calendar years.Substantial heterogeneity remained unaccounted for throughout the analyses, even after accounting for hypothetical contributors.This meta-analysis revealed substantial regional differences in antidepressant use around pregnancy, which could be due to variability in prescription behavior, healthcare seeking behavior and organization of healthcare. There is an urgent need for evidence on effectiveness, benefit, and harm of antidepressants during pregnancy to guide clinical practice.

Despite increased prevalence of domestic violence and abuse (DVA), victimization through DVA often remains undetected in mental health care. To estimate the effectiveness of a system provider level training intervention by comparing the detection and referral rates of DVA of intervention community mental health (CMH) teams with rates in control CMH teams. We also aimed to determine whether improvements in knowledge, skills and attitudes to DVA were greater in clinicians working in intervention CMH teams than those working in control teams. We conducted a cluster randomized controlled trial in two urban areas of the Netherlands. Detection and referral rates were assessed at baseline and at 6 and 12 months after the start of the intervention. DVA knowledge, skills and attitudes were assessed using a survey at baseline and at 6 and 12 months after start of the intervention. Electronic patient files were used to identify detected and referred cases of DVA. Outcomes were compared between the intervention and control teams using a generalized linear mixed model. During the 12-month follow-up, detection and referral rates did not differ between the intervention and control teams. However, improvements in knowledge, skills and attitude during that follow-up period were greater in intervention teams than in control teams: β 3.21 (95% CI 1.18-4.60). Our trial showed that a training program on DVA knowledge and skills in CMH teams can increase knowledge and attitude towards DVA. However, our intervention does not appear to increase the detection or referral rates of DVA in patients with a severe mental illness. A low detection rate of DVA remains a major problem. Interventions with more obligatory elements and a focus on improving communication between CMH teams and DVA services are recommended.The trial has been registered on the ISRCTN register, number: ISRCTN14115257.

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.

Gastroesophageal reflux (GER), excessive crying, and constipation are common gastrointestinal symptoms in infancy of multifactorial origin in which psychosocial stress factors play an important role. The aims of this observational study were to investigate the presence of gastrointestinal symptoms in infants of mothers with or without a history of a psychiatric disorder, their association with maternal depressive symptoms, and the possible mediating role of bonding.One hundred one mothers with a history of a psychiatric disorder and 60 control mothers were included. Infant gastrointestinal symptoms, maternal depressive symptoms, and mother-infant bonding were assessed using validated questionnaires and diagnostic criteria at 1.5 months postpartum.The mean total score on the Infant Gastroesophageal Reflux Questionnaire Revised reported in infants of mothers with psychiatric disorder (13.4 standard deviation 5.4) was significantly higher than that in infants of control mothers (10.8 standard deviation 5.4; P = .003). No significant differences were found in the presence of excessive crying (modified Wessel criteria and subjective experience) and constipation (ROME IV criteria) between both groups. Infant GER was associated with maternal depressive symptoms (P = 0.027) and bonding problems (P = 0.001). Constipation was related to maternal depressive symptoms (P = 0.045), and excessive crying (Wessel and subjective criteria) was associated with bonding problems (P = 0.022 and P = 0.002, respectively). The effect of maternal depressive symptomatology on infant GER symptoms and excessive crying was mediated by bonding problems.Maternal psychiatric history is associated with infant gastrointestinal symptoms, in which mother-infant bonding is a mediating factor.

Objective Although cross-sectional studies have shown that the COVID-19 pandemic has negativelyaffected the mental health of adolescents, the effect of the pandemic on adolescents with pre-pandemicsymptoms is unclear. We therefore tested the hypothesis that adolescents had increased emotional andbehavioral problems during the lockdowns imposed during the pandemic.Method This study included three measurements in a prospective cohort of 1022 adolescentswho were oversampled based on their high risk of developing psychopathology. Before the pandemic, weassessed depressive, anxiety, stress, oppositional defiant problems, psychotic experiences and suicidality,using the Youth Self-Report; 445 and 333 of these 1022 adolescents subsequently completed the onlinequestionnaire in the first lockdown (in April 2020) and in the second lockdown (in January 2021),respectively. Multilevel random intercept regression models were used to determine the change inpsychiatric symptoms, including an interaction term to assess whether these changes differed based onthe severity of symptoms prior to the pandemic.Results Throughout the pandemic, the majority of adolescents reported having emotional and behavioralsymptoms that were within the normal range. Moreover, the mean symptom scores for all six outcomesdecreased significantly among adolescents with high clinical severity prior to the pandemic.Conclusion In contrast to our original hypothesis, the effects of the COVID-19 pandemic may notnecessarily be detrimental, at least among a specific subgroup of adolescents with preexisting mentalhealth problems. Moreover, our finding that most adolescents did not report experiencing clinicallyrelevant symptoms during the pandemic reflects their resilience during the pandemic.

Objective We aimed to investigate the outcome of postpartum psychosis over a four-year follow-up, and to identify potential clinical markers of mood/psychotic episodes outside of the postpartum period. Methods One hundred and six women with a diagnosis of first-onset mania or psychosis during the postpartum period were included in this prospective longitudinal study. Women were categorized into either (1) recurrence of non-postpartum mood/psychotic episodes or (2) mania/psychosis limited to the postpartum period. We summarize the longitudinal course of the illness per group. We used a logistic regression model to identify clinical predictors of recurrence of mood/psychotic episodes outside of the postpartum period. Results Over two thirds of the women included in this study did not have major psychiatric episodes outside of the postpartum period during follow-up. The overall recurrence rate of mood/psychotic episodes outside the postpartum period was ~ 32%. Of these women, most transitioned to a bipolar disorder diagnosis. None of the women fulfilled diagnostic criteria for schizophrenia or schizophreniform disorder. No clinical markers significantly predicted recurrence outside of the postpartum period. Conclusions For the majority of women with first-onset postpartum psychosis, the risk of illness was limited to the period after childbirth. For the remaining women, postpartum psychosis was part of a mood/psychotic disorder with severe non-postpartum recurrence, mainly in the bipolar spectrum. No clinical predictors for risk of severe episodes outside the postpartum period emerged. Our findings add to previous evidence suggesting a fundamental link between postpartum psychosis and bipolar disorder, which may represent two distinct diagnoses within the same spectrum.

Background. Maternal psychopathology is associated with altered HPA axis functioning in offspring. Most studies have focused on mildly affected populations, but less is known about the effect of severe maternal psychopathology. In our explorative study we investigated in a heterogenic sample of mothers with severe and long-lasting psychiatric disorders, if a diagnosis of depression and severity of general maternal psychiatric symptomatology were associated with infant salivary cortisol reactivity to the Face-to-Face Still-Face (FFSF) paradigm at 6 months of age. Methods. A clinical sample of 36 mother-infant dyads was explored. All mothers fulfilled criteria for a severe psychiatric disorder and had psychiatric complaints for the last two consecutive years. Maternal diagnosis was established during pregnancy using a diagnostic interview and general maternal psychiatric symptom severity was established by self-report at the time of the FFSF procedure. The FFSF paradigm was used to assess infants’ response to social stress at the age of 6 months. Infant saliva samples were collected at three time points: 5 min before and 15 and 30 min after the social stressor. Cortisol reactivity was operationalized as incremental Area Under the Curve (AUCi). Potential confounders were identified and adjusted for. Results. In regression analyses, a negative relationship was found between infant cortisol reactivity (AUCi) during the FFSF paradigm at 6 months and general maternal symptom severity at time of the FFSF paradigm (unadjusted n = 36, s = −0.331, B = −9.758, SE 4.8, p = .048; adjusted n = 36, s = −0.335, B = −9.868, SE 4.5, p = .039) and for diagnosis of perinatal depression at trend level (unadjusted n = 36, s = −0.293, B = −8.640, SE 4.8, p = .083; adjusted n = 36, s = −0.317, B = −9.347, SE 4.6, p = .052). Analyses were adjusted for gestational age. Conclusions. Preliminary results on cortisol reactivity in 6-month-old infants of mothers with severe and long-lasting psychiatric disorders show a significant reduction in the group of mothers who experienced a high level of psychiatric symptoms in the post-partum period, compared to mothers with lower levels of psychiatric symptomatology. The same trend was found for mothers with and without a diagnosis of perinatal depression. Since these infants are considered to be at increased risk for later psychopathology, our study suggests that future longitudinal studies should investigate whether reduced cortisol reactivity in babies could be a marker for any adverse outcomes, besides other possible risk factors (e.g. (epi)genetic phenomena).

Objectives: The authors sought to evaluate the impact of ischemic burden reduction after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on long-term prognosis and cardiac symptom relief. Background: The clinical benefit of CTO PCI is questioned. Methods: In a high-volume CTO PCI center, 212 patients prospectively underwent quantitative [ 15O]H 2O positron emission tomography perfusion imaging before and three months after successful CTO PCI between 2013-2019. Perfusion defects (PD) (in segments) and hyperemic myocardial blood flow (hMBF) (in ml · min −1 · g −1) allocated to CTO areas were related to prognostic outcomes using unadjusted (Kaplan-Meier curves, log-rank test) and risk-adjusted (multivariable Cox regression) analyses. The prognostic endpoint was a composite of all-cause death and nonfatal myocardial infarction. Results: After a median [interquartile range] of 2.8 years [1.8 to 4.3 years], event-free survival was superior in patients with ≥3 versus −1 · g −1) versus below the population median (p < 0.01; risk-adjusted p < 0.01; HR: 0.16 [95% CI: 0.05 to 0.54]) after CTO PCI. Furthermore, event-free survival was superior in patients without versus any residual PD (p < 0.01; risk-adjusted p = 0.02; HR: 0.22 [95% CI: 0.06 to 0.76]) or with a residual hMBF level >2.3 versus ≤2.3 ml · min −1 · g −1 (p < 0.01; risk-adjusted p = 0.03; HR: 0.25 [95% CI: 0.07 to 0.91]) at follow-up positron emission tomography. Patients with residual hMBF >2.3 ml · min −1 · g −1 were more frequently free of angina and dyspnea on exertion at long-term follow-up (p = 0.04). Conclusions: Patients with extensive ischemic burden reduction and no residual ischemia after CTO PCI had lower rates of all-cause death and nonfatal myocardial infarction. Long-term cardiac symptom relief was associated with normalization of hMBF levels after CTO PCI.

Background Maternal psychopathology during pregnancy is associated with negative outcomes in offspring. Increased placental transfer of maternal cortisol may contribute to mediate this association. Hair cortisol concentrations (HCCs) appear to be a good biomarker of long-term prenatal stress exposure. Little is known about the associations between severe maternal psychopathology and perinatal infant HCCs. Aims We assessed HCCs in the perinatal period in mother–infant dyads with and without severe psychiatric disorders. Method We examined group differences in HCCs of mother–infant dyads (n = 18) subjected to severe maternal psychiatric disorders versus healthy control dyads (n = 27). We assessed the correlation of HCCs between mother and infant within both groups, and the association between current maternal symptoms and HCCs in patient dyads. Results Median (interquartile range) and distribution of HCC differed in patients compared with control mothers (U = 468.5, P = 0.03). HCCs in infants of patients did not differ from control infants (U = 250.0, P = 0.67). Subsequently, we found that HCCs within healthy control dyads were correlated (n = 27, r 0.55 (0.14), P = 0.003), but were not within patient dyads (n = 18, r 0.082 (0.13), P = 0.746). HCCs in infants of patients showed a positive correlation with maternal symptoms (n = 16, r = 0.63 (0.06), P = 0.008). Conclusions These preliminary findings suggest that infant HCC reflect perinatal stress exposure. In infants, these early differences could influence lifetime hypothalamic–pituitary–adrenal axis functioning, which might be associated with increased susceptibility to later disease.

Background Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) leads to major reductions in ischemic burden. However, to date, studies investigating if more ischemia reduction after CTO PCI translates into an improved patient prognosis, are lacking. Purpose To evaluate if change in absolute myocardial perfusion after CTO PCI is related to patient prognosis. Methods Between 2013–2019, 219 prospectively recruited patients with a CTO underwent quantitative [15O]H2O positron emission tomography perfusion imaging before and 3 months after successful CTO PCI in a single high-volume CTO PCI center (175 procedures/year). Changes in perfusion defect size (in myocardial segments) and hyperemic myocardial blood flow (MBF, in mL min–1 g–1) within the CTO territory after PCI were related to the combined endpoint of death or myocardial infarction (MI). Kaplan-Meier curves (log-rank test) and multivariable Cox regression (including covariates age, gender, prior MI, and left ventricular function) were used to analyze unadjusted and risk-adjusted event-free survivals with HR [95% CI]. Results Out of 213 (97%) patients with a median follow-up of 3.2 [2.1–4.7] years, 22 (10%) patients experienced the composite of death (19, 9%) or MI (5, 2%). Event-free survival was significantly improved in patients with a perfusion defect size reduction of ≥3 segments (N=132, 62%) after CTO PCI compared to 1.13 mL min–1 g–1) as compared to below the median (p2.30 mL min–1 g–1 (N=105, 49%) showed a better event-free survival compared to patients with lower residual hyperemic MBF levels (p=0.02, risk-adjusted: p=0.04 with HR 0.33 [0.12–0.95]). Conclusions Patients with more ischemic burden reduction and less residual ischemia following CTO PCI showed a major improved survival free of death or MI. A limitation was the low absolute number of events that prohibited more extensive risk-adjustment of the analyses. Funding Acknowledgement Type of funding source: None

Summary:. Hyperbaric oxygen therapy (HBOT) serves as “primary” or “adjunctive” therapy in a wide range of pathologies. It is considered the mainstay of management for potentially life-threatening conditions such as carbon monoxide poisoning, decompression illness, and gas embolisms. Moreover, HBOT has been utilized for decades as an adjunctive therapy in a variety of medical disciplines, including chronic wounds, which affect approximately 6.5 million Americans annually. In general, chronic wounds are characterized by hypoxia, impaired angiogenesis, and prolonged inflammation, all of which may theoretically be ameliorated by HBOT. Nonetheless, the cellular, biochemical, and physiological mechanisms by which HBOT achieves beneficial results in chronic wounds are not fully understood, and there remains significant skepticism regarding its efficacy. This review article provides a comprehensive overview of HBOT, and discusses its history, mechanisms of action, and its implications in management of chronic wounds. In particular, we discuss the current evidence regarding the use of HBOT in diabetic foot ulcers, while digging deeply into the roots of controversy surrounding its efficacy. We discuss how the paucity of high-quality research is a tremendous challenge, and offer future direction to address existing obstacles.

Mother-to-infant bonding is important for long-term child development. The aim of this study was to investigate bonding in women admitted to a Mother and Baby Unit with postpartum depression (PD, n = 64) and postpartum psychosis (PP, n = 91). Participants completed the Postpartum Bonding Questionnaire (PBQ), the Edinburgh Postnatal Depression Scale (EPDS) and the Young Mania Rating Scale (YMRS) weekly during admission. At admission, 57.1% of women with PD had impaired bonding, compared to only 17.6% of women with PP (p-value < 0.001). At discharge, only 18.2% of women with PD and 5.9% of women with PP still experienced impaired bonding (p-value = 0.02). There was a strong association between decrease of depressive and manic symptoms and improved bonding over an eight-week admission period. In a small group of women (5.7%) impaired bonding persisted despite being in remission of their psychiatric disorder. The results from our study show that impaired bonding is a more present and evidently severe problem in postpartum depression but not so much in postpartum psychosis. Treatment of depressive symptoms will improve bonding in almost all women, but clinicians should assess if impaired bonding is still present after remission because for a small group special care and treatment focused on bonding might be required.

Recent studies have provided new data on the teratogenicity of lithium. Less is known about the risk of miscarriage after lithium use during pregnancy. The aim of this study was to investigate the association between lithium use during pregnancy and miscarriage. Participants were women with bipolar I disorder and one or more pregnancies, of which information on medication use and pregnancy outcome was available (n = 443). The unadjusted odds ratios for miscarriage after lithium use during pregnancy was calculated. Multilevel logistic regression was used to calculate the odds ratio, adjusted for the age at conception and the clustering of pregnancies per woman. Miscarriages occurred in 20.8% of the lithium-exposed pregnancies (16/77), compared with 10.9% of the unexposed pregnancies (40/366) (OR = 2.14; 95% CI: 1.13–4.06). The adjusted odds ratio of miscarriage after lithium use during pregnancy was 2.94 (95% CI: 1.39–6.22). Lithium use during pregnancy may increase the risk of miscarriage.

To investigate whether older age predicts a higher efficacy of electroconvulsive therapy (ECT) in severely depressed patients. Also, to analyze whether psychomotor disturbance and/or psychotic features might explain the potential higher efficacy of ECT in older age.A total of 96 patients with major depressive disorder treated with bilateral ECT were evaluated. The 17-item HAM-D and the MADRS were used to evaluate the efficacy of ECT and time to remission, respectively. Psychomotor disturbance was defined according the HAM-D.Middle-aged (MA; 50-70 years) and older-aged (OA; ≥70 years) patients had a non-significant larger symptom reduction compared with young-aged (YA;50 years) patients. Medium effect size was found in favor of MA (d = 0.44) and small effect size in favor of OA (d = 0.30), when compared to YA. Patients with psychotic features and patients with psychomotor retardation had a significantly larger symptom reduction (p 0.001 and p = 0.005, respectively; d = 0.88 and d = 0.66, respectively). The association between age and ECT efficacy is mediated by psychomotor retardation (p = 0.049) and in lesser extent by psychotic features (p = 0.071).The results show that psychomotor retardation and psychotic features are strong predictors of ECT efficacy and explain the association between age and ECT efficacy. Instead of focusing on the age of a patient, clinicians should focus on the presence of psychomotor disturbances and psychotic features of depression, when considering ECT treatment.

Objective: To investigate whether early improvement, measured after two electroconvulsive therapy (ECT) sessions, is a good predictor of eventual remission in severely depressed in-patients receiving ECT. Method: A prospective cohort study was performed that included 89 major depressive disorder in-patients treated with bilateral ECT. Sensitivity, specificity, and predictive values were computed for various definitions of early improvement (15%, 20%, 25%, and 30% reduction on the Montgomery Asberg depression rating scale (MADRS) score) after 1 week (i.e. two sessions) of ECT regarding prediction of remission (final MADRS score ≤ 9). Results: A 15% reduction in MADRS score appeared to be the best definition of early improvement, with modest sensitivity (51%) and relatively good specificity (79%). Kaplan–Meier analysis showed a more than 2-week shorter time to remission in patients with early improvement compared with patients lacking early improvement. Conclusion: Early improvement during an ECT course may be assessed after two ECT sessions. Such improvement, defined as a 15% reduction in the MADRS score, is a moderately sensitive predictor for eventual remission in an in-patient population with severe major depression.

OBJECTIVE: There is limited information on the longitudinal disease course after first-onset postpartum psychosis (PP). Some women will experience severe affective episodes outside the postpartum period, while for other women their vulnerability to mania and psychosis may be restricted to the postpartum period. This meta-analysis estimates the risk of recurrence after first-onset PP. DATA SOURCES: A computerized literature search was conducted using Embase, MEDLINE, Web of Science, PsycINFO, Cochrane Central, PubMed, and Google Scholar (first 100 hits) combining key terms regarding longitudinal studies of first-onset PP from inception through May 9, 2019. Two levels of screening were used on 2,807 citations. STUDY SELECTION: A total of 6 English-language articles including patients with a first-onset PP within 1 year after childbirth and a minimum follow-up period of 18 months or more after the index episode were included in the quantitative analysis. DATA EXTRACTION: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were used for data extraction, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were used to independently assess the quality of the included studies. The primary outcome was recurrence, defined as any subsequent psychiatric episode after first-onset PP. RESULTS: Six studies and 645 patients could be included in the quantitative analyses; follow-up periods were 11-26 years. Of these patients, 279 did not experience subsequent severe episodes outside the postpartum period. Meta-analysis using random-effect estimation resulted in a weighted estimate of 43.5% (95% CI, 37.7% to 49.4%). CONCLUSIONS: In this meta-analysis, more than 40% of women were classified as having "isolated postpartum psychosis," which could be considered a distinct diagnostic category with a more favorable prognosis. The remaining women had severe non-puerperal psychiatric episodes during longitudinal follow-up.

OBJECTIVE: Several clinical variables assumed to be predictive of electroconvulsive therapy (ECT) outcome in major depressive disorder show substantial interrelations. The current study tries to disentangle this interdependence to distill the most important predictors of treatment success to help improve patient-treatment matching. METHODS: We constructed a conceptual framework of interdependence capturing age, episode duration, and treatment resistance, all variables associated with ECT outcome, and the clinical symptoms of what we coin core depression, ie, depression with psychomotor agitation, retardation, psychotic features, or a combination of the three. The model was validated in a sample of 73 patients with a major depressive episode according to DSM-5 treated twice weekly with ECT (August 2015-January 2018) using path analyses, with the size and direction of all direct and indirect paths being estimated using structural equation modeling. Reduction in Montgomery-Asberg Depression Rating Scale (MADRS)scores during treatment was the ECT outcome measure. RESULTS: The baseline presence of psychomotor agitation, retardation, and/or psychotic symptoms strongly correlated with beneficial ECT outcome (z = 0.84 [SE = 0.17]; P < .001), and the association between age and the effect of ECT appears to be mediated by their presence (z = 0.53 [SE = 0.18]; P = .004). There was no direct correlation between age and ECT response (P = .479), but there was for episode duration and ECT outcome (z = -0.38 [SE = 0.08]; P < .001). CONCLUSIONS: ECT is a very effective treatment option for severe depressive disorder, especially for patients suffering from severe depression characterized by the presence of psychomotor agitation, psychomotor retardation, psychotic symptoms, or a combination of these 3 features, with the chance of a beneficial outcome being reduced in patients with a longer episode duration. Age may heretofore have been given too much weight in ECT decision making. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02562846.

Objective:Several countries have developed Clinical Practice Guidelines regarding treatment of perinatal depressive symptoms and perinatal use of antidepressant. We aimed to compare guidelines to guide clinicians in best clinical practice.Methods:An extensive search in guideline databases, MEDLINE and PsycINFO was performed. When no guidelines were (publicly) available online, we contacted psychiatric-, obstetric-, perinatal- and mood disorder societies of all first world countries and the five largest second world countries. Only Clinical Practice Guidelines adhering to quality criteria of the Appraisal of Guidelines for Research and Evaluation instrument and including a systematic review of evidence were included. Data extraction focussed on recommendations regarding continuation or withdrawal of antidepressants and preferred treatment in newly depressed patients.Results:Our initial search resulted in 1094 articles. After first screening, 40 full-text articles were screened. Of these, 24 were excluded for not being an official Clinical Practice Guidelines. In total, 16 Clinical Practice Guidelines were included originating from 12 countries. Eight guidelines were perinatal specific and eight were general guidelines.Conclusion:During pregnancy, four guidelines advise to continue antidepressants, while there is a lack of evidence supporting this recommendation. Five guidelines do not specifically advise or discourage continuation. For new episodes, guidelines agree on psychotherapy (especially cognitive behavioural therapy) as initial treatment for mild to moderate depression and antidepressants for severe depression, with a preference for sertraline. Paroxetine is not preferred treatment for new episodes but switching antidepressants for ongoing treatment is discouraged (three guidelines). If mothers use antidepressants, observation of the neonate is generally recommended and breastfeeding encouraged.

Lithium and antipsychotics are often prescribed to treat bipolar disorder or psychotic disorders in women of childbearing age. Little is known about the consequences of these medications during pregnancy for the developing child. The objective of this article is to systematically review findings from preclinical and clinical studies that have examined the neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics. A systematic search was performed in Embase, Medline, Web of Science, PsychINFO, Cochrane, and Google Scholar. Clinical and experimental studies were selected if they investigated neurodevelopment of offspring exposed to lithium or antipsychotics during gestation. Quality of clinical and preclinical studies was assessed by the Newcastle–Ottawa Scale and the SYRCLE’s risk of Bias tool, respectively. In total, 73 studies were selected for qualitative synthesis and three studies were selected for quantitative synthesis. Of preclinical studies, 93% found one or more adverse effects of prenatal exposure to antipsychotics or lithium on neurodevelopment or behaviour. Only three clinical cohort studies have investigated the consequences of lithium exposure, all of which reported normal development. In 66% of clinical studies regarding antipsychotic exposure, a transient delay in neurodevelopment was observed. The relative risk for neuromotor deficits after in utero exposure to antipsychotics was estimated to be 1.63 (95% CI 1.22–2.19; I2 = 0%). Preclinical studies suggest long-term adverse neurodevelopmental consequences of intrauterine exposure to either lithium or antipsychotics. However, there is a lack of high-quality clinical studies. Interpretation is difficult, since most studies have compared exposed children with their peers from the unaffected population, which did not allow correction for potential influences regarding genetic predisposition or parental psychiatric illness.

BackgroundDuring the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to investigate the association between TPO-ab status during early gestation and first-onset postpartum depression.MethodsProspective cohort study (n = 1075) with follow-up during pregnancy up to one year postpartum. Thyroid function and TPO-ab status were measured during early gestation. Depressive symptomatology was assessed during each trimester and at four time points postpartum with the Edinburgh Depression Scale (EDS). Women with antenatal depression were not eligible for inclusion. Self-reported postpartum depression was defined with an EDS cut-off of ≥ 13.ResultsThe cumulative incidence of self-reported first-onset depression in the first postpartum year was 6.3%. A positive TPO-ab status was associated with an increased risk for self-reported first-onset depression at four months postpartum (adjusted OR 3.8; 95% CI 1.3–11.6), but not at other postpartum time points. Prevalence rates of self-reported postpartum depression declined after four months postpartum in the TPO-ab positive group, but remained constant in the TPO-ab negative group.LimitationsDepression was defined with a self-rating questionnaire (EDS).ConclusionsWomen with an increased TPO-ab titer during early gestation are at increased risk for self-reported first-onset depression. The longitudinal pattern of self-reported postpartum depression in the TPO-ab positive group was similar to the typical course of postpartum TPO-ab titers changes. This suggests overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. Thyroid function should be evaluated in women with first-onset postpartum depression.

Background Maternal use of benzodiazepines during pregnancy is common and has increased over the last decades. In this systematic review and meta-analysis, we studied the literature to estimate the worldwide use of benzodiazepines before, during and after pregnancy, which could help to estimate benzodiazepine exposure and to prioritize and guide future investigations. Methods We systematically searched Embase, Medline Ovid, Web of Science and Cochrane Central up until July 2019 for studies reporting on benzodiazepine use before (12 months), during and after pregnancy (12 months). Random effects meta-analysis was conducted to calculate pooled prevalence estimates, as well as stratified according to substantive variables. Results We identified 32 studies reporting on 28 countries, together reporting on 7,343,571 pregnancies. The worldwide prevalence of benzodiazepine use/prescriptions during pregnancy was 1.9% (95%CI 1.6%-2.2%; I2 97.48%). Highest prevalence was found in the third trimester (3.1%; 95%CI 1.8%-4.5%; I2 99.83%). Lorazepam was the most frequently used/prescribed benzodiazepine (1.5%; 95%CI 0.5%-2.5%; I2 99.87%). Highest prevalence was found in Eastern Europe (14.0%; 95%CI 12.1%-15.9%; I2 0.00%). Limitations All analyses revealed considerable heterogeneity. Conclusions Our meta-analysis confirmed that benzodiazepine use before, during and after pregnancy is prevalent. The relatively common use of benzodiazepines with possible risks for both mother and (unborn) child is worrying and calls for prescription guidelines for women, starting in the preconception period. Given the substantial proportion of children exposed to benzodiazepines in utero, future research should continue to study the short- and long-term safety of maternal benzodiazepine use during pregnancy and to explore non-pharmacological alternative treatments.

ObjectivesApproximately 11%–13% of pregnant women suffer from depression. Bright light therapy (BLT) is a promising treatment, combining direct availability, sufficient efficacy, low costs and high safety for both mother and child. Here, we examined the effects of BLT on depression during pregnancy.DesignRandomised, double-blind controlled trial.SettingPrimary and secondary care in The Netherlands, from November 2016 to March 2019.Participants67 pregnant women (12–32 weeks gestational age) with a DSM-5 diagnosis of depressive disorder (Diagnostic and Statistical Manual of Mental Disorders).InterventionsParticipants were randomly allocated to treatment with either BLT (9000 lux, 5000 K) or dim red light therapy (DRLT, 100 lux, 2700 K), which is considered placebo. For 6 weeks, both groups were treated daily at home for 30 min on awakening. Follow-up took place weekly during the intervention, after 6 weeks of therapy, 3 and 10 weeks after treatment and 2 months postpartum.Primary and secondary outcome measuresDepressive symptoms were measured primarily with the Structured Interview Guide for the Hamilton Depression Scale—Seasonal Affective Disorder. Secondary measures were the Hamilton Rating Scale for Depression and the Edinburgh Postnatal Depression Scale. Changes in rating scale scores of these questionnaires over time were analysed using generalised linear mixed models.ResultsMedian depression scores decreased by 40.6%–53.1% in the BLT group and by 50.9%–66.7% in the DRLT group. We found no statistically significant difference in symptom change scores between BLT and DRLT. Sensitivity and post-hoc analyses did not change our findings.ConclusionsDepressive symptoms of pregnant women with depression improved in both treatment arms. More research is necessary to determine whether these responses represent true treatment effects, non-specific treatment responses, placebo effects or a combination hereof.Trial registration numberNTR5476.

Background Premenstrual syndrome is characterized by the cyclic occurrence of physical, behavioral and psychological symptoms during the luteal phase of the menstrual cycle disappearing within a few days of the onset of menstruation. Generally symptoms are mild, but 5–8% of women suffer from severe PMS. Apart from conventional drugs, like serotonin reuptake inhibitors and oral contraceptives, complementary and alternative medicines such as Vitex agnus castus are used by many women experiencing PMS. Objective Our objective was to determine the efficacy, tolerability, and acceptability of Vitex agnus castus preparations for treatment of premenstrual syndrome. Study Design All journals in the Ovid software from inception through January 2016 were searched, including the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and PsycINFO. Gray literature was searched by Google Scholar and manufacturers of Vitex agnus castus preparations were contacted for information about unpublished trials. We included randomized controlled trials with Vitex agnus castus in women with premenstrual syndrome and/or premenstrual dysphoric disorder with a minimal duration of 2 menstrual cycles. The eligibility of the manuscripts was assessed by 2 reviewers independently. The data abstracted included characteristics of the study design, characteristics of the patient population, intervention details, type of comparator, method of diagnosis, and outcome measures. We adhered to the PRISMA guidelines. Results We found 17 randomized controlled trials of Vitex agnus castus in the treatment of premenstrual syndrome. Fourteen of these could be included in the quantitative analysis. Thirteen of 14 studies with placebo, dietary supplements, or herbal preparations as controls reported positive effects of Vitex agnus castus on total premenstrual syndrome symptoms. Unfortunately most of the trials are associated with a high risk of bias. The pooled effect of Vitex agnus castus in placebo-controlled trials was large (Hedges g, –1.21; 95% confidence interval, –1.53 to –0.88), but heterogeneity was extremely high (I 2 , 91%). We were unable to single out factors that could explain this heterogeneity satisfactorily. The funnel plot and Egger tests suggest the presence of publication bias. Conclusion Although meta-analysis shows a large pooled effect of Vitex agnus castus in placebo-controlled trials, the high risk of bias, high heterogeneity, and risk of publication bias of the included studies preclude a definitive conclusion. The pooled treatment effects should be viewed as merely explorative and, at best, overestimating the real treatment effect of Vitex agnus castus for premenstrual syndrome symptoms. There is a clear need for high-quality trials of appropriate size examining the effect of standardized extracts of Vitex agnus castus in comparison to placebo, selective serotonin reuptake inhibitors, and oral contraceptives to establish relative efficacy.

__Objective:__ Postpartum psychosis is an acute and severe mood disorder. Although the prognosis is generally good, postpartum psychosis is a highly stressful life-event presumed to have a major impact on functioning and well-being beyond the acute stage of the illness. We studied functional recovery, including psychosocial functioning and the presence of psychological distress, in patients with a recent diagnosis of postpartum psychosis. __Methods:__ Seventy-eight patients with postpartum psychosis consecutively admitted for inpatient hospitalization between 2005 and 2011 were assessed 9 months postpartum. Included were patients with DSM-IV-TR diagnoses of psychotic disorder not otherwise specified, brief psychotic disorder, or mood disorder with psychotic features, each requiring the additional specifier “with postpartum onset.” Functioning was assessed in 4 domains by the Longitudinal Interval Follow-up Evaluation–Range of Impaired Functioning Tool (LIFE-RIFT). Symptomatology was measured by the Brief Symptom Inventory and compared to a matched population-based cohort. __Results:__ Nine months postpartum, 74% (58/78) of women with postpartum psychosis reported good functioning on the domains of work, interpersonal relations, recreation, and global satisfaction. Moreover, 88% (69/78) of patients with postpartum psychosis had resumed their premorbid employment and household responsibilities. Compared to the general population, patients with postpartum psychosis reported a higher burden of depression and anxiety (effect sizes r ≤ 0.14). Patients who had a relapse episode (18%) experienced considerable functional impairments across several domains. __Conclusions:__ Nine months postpartum, the majority of patients with postpartum psychosis reported good functional recovery. Our relatively improved functional outcomes compared to nonpostpartum onset could be attributed to the postpartum onset and/or more favorable risk factor profile.

Objectives Postpartum psychosis (PP) is known for its clear onset but its phenotype has never been clearly described in a cohort. The aim of this study was to describe PP symptomatology, and to identify subgroups of patients based on symptom profiles. Methods We prospectively assessed a wide range of symptoms in cases of PP in a cohort of women (N=130) admitted to the Mother-Baby inpatient unit. Using a person-centered analytic approach, we distinguished mutually exclusive subgroups of women. Subgroups were related to demographic and clinical characteristics. Results The most prevalent symptoms of PP were irritability (73%), abnormal thought content (72%), and anxiety (71%). Suicidal and infanticidal ideation was present in 19% and 8% of patients, respectively. Delusions and hallucinations often had a negative content. Latent class analysis revealed three symptom profiles, a manic (34%), depressive (41%) and atypical (25%) profile, respectively. The manic profile is characterized by manic symptoms and agitation, the depressive profile by depressive and anxiety symptoms, and the atypical profile by disturbance of consciousness and disorientation. In women with a depressive profile, treatment was started 2 weeks later (P=.049), and more often voluntarily, than in manic and atypical women (P=.037). Conclusions We distinguished subgroups of PP patients with a manic, depressive, and atypical profile. Disturbance of consciousness, disorientation, and depersonalization/derealization were less prevalent than previously suggested in the literature. Instead, the depressive profile was the most prevalent, but the depressive profile can easily remain undetected, which could lead to treatment delay and risk of suicide/infanticide. Within the manic profile, irritability was highly prevalent and occurred more often than elevated mood.

ObjectiveAntidepressant 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.MethodsEighty-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.ResultsEight 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).ConclusionImplementing 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.

Objective: Using outcome data collected routinely over a continuous two-year treatment period, we wished to distinguish homogeneous subgroups of patients with a severe mental illness whose psychosocial problems followed a similar pattern over time. By identifying the effectiveness of health services for different patient groups, this approach allowed us to identify patients at risk of deterioration and those recovering from their symptoms.Methods: In total we included 2,660 patients who were in two-year continuous contact with a Flexible Assertive Community Treatment team (FACT). We collected outcome data on psychosocial functioning, needs for care and quality of life. We performed a latent class growth analysis (LCGA).Results: The LCGA identified six homogenous patient subgroups using trajectories of HoNOS scores. On the basis of the patterns of patients’ psychosocial problems over time, we labelled these as follows: 1) stable at a low problem-severity level (N = 709; 27%); 2) stable at a low medium problem-severity level (N = 1,208; 45%); 3) stable at a high medium problem-severity level (N = 528; 20%); 4) stable at a high problem-severity level (N = 116; 4%); 5) amelioration of problems (N = 42; 2%); and 6) deterioration of problems (N = 57; 2%). Patients with stable and a high severity of psychosocial problems had more practical and somatic unmet needs than those in other subgroups, and also had the fewest decrease in the number of unmet needs.Discussion: After linking patient subgroups with clinical features such as the need for care, we found that, over two years, most patients remained relatively stable in terms of psychosocial functioning, but that their unmet needs decreased over time. However, in terms of needs for treatment during two years of contact with a FACT team, patients in the subgroup with a stable and high problem-severity level tended to derive little or no benefit.

Objective:Women with a history of bipolar disorder, postpartum psychosis, or both are at high risk for postpartum relapse. The aim of this meta-analysis was to estimate the risk of postpartum relapse in these three patient groups.Method:A systematic literature search was conducted in all public medical electronic databases, adhering to the PRISMA guidelines. Studies were included if they reported postpartum relapse in patients diagnosed with bipolar disorder and/or a history of postpartum psychosis or mania according to DSM or ICD criteria or the Research Diagnostic Criteria.Results:Thirty-seven articles describing 5,700 deliveries in 4,023 patients were included in the quantitative analyses. The overall postpartum relapse risk was 35% (95% CI=29, 41). Patients with bipolar disorder were significantly less likely to experience severe episodes postpartum (17%, 95% CI=13, 21) than patients with a history of postpartum psychosis (29%, 95% CI=20, 41). Insufficient information was available to determine relapse rates for patients with bipolar disorder and a history of postpartum episodes. In women with bipolar disorder, postpartum relapse rates were significantly higher among those who were medication free during pregnancy (66%, 95% CI=57, 75) than those who used prophylactic medication (23%, 95% CI=14, 37).Conclusions:One-third of women at high risk experience a postpartum relapse. In women with bipolar disorder, continuation of prophylactic medication during pregnancy appears highly protective for maintaining mood stability postpartum. In women with a history of isolated postpartum psychosis, initiation of prophylaxis immediately after delivery offers the opportunity to minimize the risk of relapse while avoiding in utero medication exposure.

Background Depressive symptoms in pregnant women, which are common and debilitating, are often co-morbid with other mental disorders (e.g. anxiety and personality disorders), and related to low socioeconomic status (SES). This situation may hamper treatment outcome, which has often been neglected in previous studies on the treatment of depression during pregnancy. We developed a new group-based multicomponent treatment (GMT) comprising cognitive behavioral therapy, psycho-education and body-oriented therapy and compared the effect on depressive symptoms with individual counseling (treatment as usual, TAU) in a heterogeneous group of pregnant women with co-morbid mental disorders and/or low SES. Methods An outpatient sample from a university hospital of 158 pregnant women who met DSM-IV criteria for mental disorders were included and 99 participants were randomized to GMT or TAU from January 2010 until January 2013. The Edinburgh Depression Scale (EDS) was used at baseline, every 5 weeks during pregnancy and as the primary outcome measure of depressive symptoms at 6 weeks postpartum. Secondary outcome measures included the clinician-reported Hamilton Depression Rating Scale (HDRS), obstetric outcomes and a ‘Patient Satisfaction’ questionnaire. Results 155 participants were included the intention-to-treat (ITT)-analysis. GMT was not superior above TAU according to estimated EDS (β = 0.13, CI = − 0.46–0.71, p = 0.67) and HDRS scores (β = − 0.39, CI = − 0.82–0.05, p = 0.08) at 6 weeks postpartum. There were no differences in secondary outcomes between the GMT and TAU, nor between the randomized condition and patient-preference condition. Limitations The ability to detect an effect of GMT may have been limited by sample size, missing data and the ceiling effect of TAU. Conclusions GMT is an acceptable treatment for a heterogeneous group of pregnant women with depressive symptoms and co-morbid mental disorders and/or low SES, but not superior to TAU. Further research should focus on understanding and treating co-morbid disorders and psychosocial problems during pregnancy. Clinical trials registration Dutch trial registry, www.trialregister.nl under reference number: NTR3015.

BackgroundElectroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates.AimsTo investigate the predictive value of age, depression severity, psychotic and melancholic features for ECT response and remission in major depression.MethodA meta-analysis was conducted according to the PRISMA statement. A literature search identified recent studies that reported on at least one of the potential predictors.ResultsOf the 2193 articles screened, 34 have been included for meta-analysis. Presence of psychotic features is a predictor of ECT remission (odds ratio (OR) = 1.47,P= 0.001) and response (OR = 1.69,P< 0.001), as is older age (standardised mean difference (SMD) = 0.26 for remission and 0.35 for response (P< 0.001)). The severity of depression predicts response (SMD = 0.19,P= 0.001), but not remission. Data on melancholic symptoms were inconclusive.ConclusionsECT is particularly effective in patients with depression with psychotic features and in elderly people with depression. More research on both biological and clinical predictors is needed to further evaluate the position of ECT in treatment protocols for major depression.Declaration of interestNone.

Traditionally, the therapeutic effect of antidepressants is thought to take several weeks. However, several studies found evidence of early drug response occurring within the first 2 weeks of antidepressant treatment and that this early onset response may predict eventual treatment outcome. This study aims to investigate the predictive value of early improvement in the course of treatment with imipramine or venlafaxine in an inpatient population with severe major depression. A post hoc analysis was conducted after pooling data from two almost identical trials. The study included 149 patients with DSM-IV diagnosis major depression and a baseline score a parts per thousand yen17 on the 17-item Hamilton Rating Scale for Depression (HAM-D). Patients were randomized for double-blind treatment with either antidepressant. Early improvement (a parts per thousand yen25 % reduction on HAM-D score) was evaluated after 2 weeks and response (a parts per thousand yen50 % reduction on HAM-D score) after 6 weeks of acute treatment. Of 64 patients achieving early improvement, 38 (59 %) became responders, whereas of 85 patients not achieving early improvement, only 23 (27 %) became responders. There was a significant difference in time to response between patients achieving early improvement and patients not achieving early improvement. Early improvement is a modest sensitive predictor for eventual response. In the present study, although the sensitivity of early improvement was modest, based on the severity of clinical symptoms, a clinician treating a patient with severe major depression may seriously consider changing the treatment at an earlier stage than is presently customary.

OBJECTIVE: To examine sustainability of symptom outcomes of a 1-year phase-based trauma-focused, multimodal, and multicomponent group therapy in a day treatment program for posttraumatic stress disorder (PTSD) over an average period of 7 years. METHOD: Iranian and Afghan patients (N = 69) were assessed with self-rated symptom checklists for PTSD, anxiety, and depression symptoms before (T1), after (T2), and up to 11 years upon completion of the treatment (T3). A series of mixed model regression analyses was applied to determine the course of the measured symptoms over time. RESULTS: At T2, all symptoms were reduced, but PTSD symptoms showed the strongest reduction. The trend of symptom reduction continued up to 5 years posttreatment and was similar for all the examined symptoms. After 5 years, all symptoms started to worsen, but remained under baseline levels at T3. CONCLUSIONS: The applied treatment appears to improve mental health of the studied sample on both the short and longer term. Language: en

Background Compulsory admissions have a strong effect on psychiatric patients and represent a deprivation of personal liberty. Although the rate of such admissions is tending to rise in several Western countries, there is little qualitative research on the mental health-care process preceding compulsory admission. The objective of the study was to identify crucial factors in the mental health-care process preceding compulsory admission of adult psychiatric patients. Methods This retrospective, qualitative multiple-case study was based on the patient records of patients with severe mental illness, mainly schizophrenia and other psychotic disorders. Twenty two patient records were analyzed. Patients’ demographic and clinical characteristics were heterogeneous. All were treated by Flexible Assertive Community Treatment teams (FACT teams) at two mental health institutions in the greater Rotterdam area in the Netherlands and had a compulsory admission in a predefined inclusion period. The data were analyzed according to the Prevention and Recovery System for Monitoring and Analysis (PRISMA) method, assessing acts, events, conditions, and circumstances, failing protective barriers and protective recovery factors. Results The most important patient factors in the process preceding compulsory admission were psychosis, aggression, lack of insight, care avoidance, and unauthorized reduction or cessation of medication. Neither were health-care professionals as assertive as they could be in managing early signs of relapse and care avoidance of these particular patients. Conclusion The health-care process preceding compulsory admission is complex, being influenced by acts, events, conditions and circumstances, failing barriers, and protective factors. The most crucial factors are patients’ lack of insight and cessation of medication, and health-care professionals’ lack of assertiveness. Electronic supplementary material The online version of this article (10.1186/s12888-017-1512-y) contains supplementary material, which is available to authorized users.

Background For women suffering from an antepartum mental disorder (AMD), there is lack of evidence-based treatment algorithms due to the complicated risk-benefit analysis for both mother and unborn child. We aimed to provide a comprehensive overview of pharmacological and non-pharmacological interventions to treat AMD and performed a meta-analysis of the estimated treatment effect on the psychiatric symptoms during pregnancy. Methods MedLine, PsycINFO and Embase databases were searched by two independent reviewers for clinical trials with a control condition on treatment of women with AMD, i.e. major depressive (MDD), anxiety, psychotic, eating, somatoform and personality disorders. We inventoried the effect of the treatment, i.e. decrease of psychiatric symptoms at the end of the treatment or postpartum. We adhered to the PRISMA-protocol. Findings Twenty-nine trials were found involving 2779 patients. Trials studied patients with depressive disorders (k = 28), and anxiety disorders (k = 1). No pharmacological trials were detected. A form of psychotherapy, like Cognitive Behavioural Therapy (g = -0.61; 95%CI:-0.73 to -0.49, I2 = 0%; k = 7) or Interpersonal Psychotherapy (g = -0.67; 95%CI:-1.27 to -0.07; I2 = 79%; k = 4), holds robust benefit for pregnant women with MDD. Body-oriented interventions (g = -0.43; 95%CI:-0.61 to -0.25; I2 = 17%; k = 7) and acupuncture (g = -0.43; 95%CI:-0.80 to -0.06; I2 = 0%; k = 2) showed medium sized reduction of depressive symptoms. Bright light therapy (g = -0.59; 95%CI:-1.25 to 0.06; I2 = 0%; k = 2), and food supplements (g = -0.51; 95%CI:-1.02 to 0.01; I2 = 20%; k = 3) did not show significant treatment effects. One study was found on Integrative Collaborative Care. Conclusions This meta-analysis found a robust moderate treatment effect of CBT for MDD during pregnancy, and to a lesser extent for IPT. As an alternative, positive results were found for body-oriented interventions and acupuncture. No evidence was found for bright light therapy and food supplements. Only non-pharmacological trials on women with MDD were found. Research on a wider range of AMD is needed.

Domestic Violence and Abuse (DVA) is associated with a range of psychosocial and mental health problems. Having a psychiatric illness increases likelihood of being a victim of DVA. Despite the evidence of a high risk for DVA and the serious effects of violent victimization in psychiatric patients, detection rates are low and responses are inadequate. The aim of the BRAVE (Better Reduction trough Assessment of Violence and Evaluation) study is to improve detection of and response to DVA in psychiatric patients. In this article, we present the protocol of the BRAVE study which follows the SPIRIT guidelines. The BRAVE study is a cluster randomized controlled trial. We will include 24 community mental health teams from Rotterdam and The Hague. Twelve teams will provide care as usual and 12 teams will receive the intervention. The intervention consists of 1) a knowledge and skills training for mental health professionals about DVA, 2) a knowledge and skills training of DVA professionals about mental illness, 3) provision and implementation of a referral pathway between community mental health and DVA services. The follow up period is 12 months. Our primary outcome is the rate of detected cases of recent or any history of DVA in patients per team in 12 months. Detection rates are obtained through a systematic search in electronic patient files. Our secondary aims are to obtain information about the gain and sustainability of knowledge on DVA in mental health professionals, and to obtain insight into the feasibility, sustainability and acceptability of the intervention. Data on our secondary aims will be obtained through structured in depth interviews and a questionnaire on knowledge and attitudes on DVA. This study is the first cluster randomized controlled trial to target both male and female psychiatric patients that experience DVA, using an intervention that involves training of professionals. We expect the rate of detected cases of DVA to increase in the intervention teams. With early detection of victimization of DVA in psychiatric patients we hope to improve the mental health of psychiatric patients in the short and long term. ISRCTN:14115257 . Date of registration: 15th January 2015.

Michelle JH Verdurmen,1 Arjan C Videler,2 Astrid M Kamperman,3 David Khasho,4 Christina M van der Feltz-Cornelis4,5 1Department of Personality Disorders, GGz Breburg, Tilburg, 2Department of Geriatric Psychiatry, GGz Breburg, Tilburg, 3Department of Psychiatry, Erasmus University Medical Center, Epidemiological and Social Psychiatric Research Institute, Rotterdam, 4Clinical Center of Excellence for Body, Mind and Health, GGz Breburg, Tilburg, 5Department of Tranzo, Tilburg University, Tilburg, The Netherlands Background: Elderly patients with somatic symptom disorder (SSD) put a great burden on the health care delivery system. Cognitive behavioral therapy (CBT) is effective in adults with SSD. However, no studies have been conducted yet into CBT for SSD in later life.Objectives: We explored the feasibility of CBT for SSD in the elderly.Methods: This is a prospective pilot study comparing two outpatient specialty mental health settings for adults (

We thank Schneeberger and colleagues for their kind remarks on our study. They raise 2 issues concerning this article. First, they point to the fact that we limited our inclusions to randomized clinical trials (RCTs) to obtain the highest level of evidence, thus excluding a large part of the literature. We acknowledge that quasiexperimental and naturalistic studies may be valuable. However, RCT-derived evidence on a certain intervention will always prevail over evidence derived from quasiexperimental and naturalistic studies. This has been clearly pointed out in the discussion on community treatment orders. Second, Schneeberger et al state that inpatient interventions, such as open-door policies in psychiatric wards, lead to a reduction of compulsory measures, referring to their own research. An admission is just one point in a patient’s trajectory through mental health care, and it is an appealing idea that reducing coercion along the total mental health chain, including ward stays, might lead to less compulsory measures. [...]

Depression during pregnancy is a common and high impact disease. Generally, 5–10 % of pregnant women suffer from depression. Children who have been exposed to maternal depression during pregnancy have a higher risk of adverse birth outcomes and more often show cognitive, emotional and behavioural problems. Therefore, early detection and treatment of antepartum depression is necessary. Both psychotherapy and antidepressant medication, first choice treatments in a non-pregnant population, have limitations in treating depression during pregnancy. Therefore, it is urgent and relevant to investigate alternative treatments for antepartum depression. Bright light therapy (BLT) is a promising treatment for pregnant women with depressive disorder, for it combines direct availability, sufficient efficacy, low costs and high safety, taking the safety for the unborn child into account as well. In this study, 150 pregnant women (12–18 weeks pregnant) with a DSM-V diagnosis of depressive disorder will be randomly allocated in a 1:1 ratio to one of the two treatment arms: treatment with BLT (9.000 lux) or treatment with dim red light therapy (100 lux). Both groups will be treated for 6 weeks at home on a daily basis for 30 min, within 30 min of habitual wake-up time. Follow-up will take place after 6 weeks of therapy, 3 and 10 weeks after end of therapy, at birth and 2, 6 and 18 months postpartum. Primary outcome will be the average change in depressive symptoms between the two groups, as measured by the Structured Interview Guide for the Hamilton Depression Scale – Seasonal Affective Disorder version and the Edinburg Postnatal Depression Scale. Changes in rating scale scores of these questionnaires over time will be analysed using generalized linear mixed models. Secondary outcomes will be the changes in maternal cortisol and melatonin levels, in maternal sleep quality and gestational age, birth weight, infant behaviour, infant cortisol exposure and infant cortisol stress response. If BLT reduces depressive symptoms in pregnant women, it will provide a safe, cheap, non-pharmacological and efficacious alternative treatment for psychotherapy and antidepressant medication in treating antepartum depression, without any expected adverse reactions for the unborn child. Netherlands Trial Register NTR5476 . Registered 5 November 2015.

This study compared quality aspects of crisis plans made with the help of a patient advocate (PACP) with those of plans made with the patient's clinician (clinician crisis plan, CCP). Patients were randomized into PACP and CCP conditions. The quality of crisis plan checklist was used to compare quality aspects of PACP and CCP crisis plans. The quality scores were significantly higher in the PACP group than in the CCP group (Cohen's d = 0.78 for the quality checklist total score). Patient advocates may be important to the successful development of crisis plans. © 2012 Springer Science+Business Media New York.

Studies on group treatment of posttraumatic stress disorder (PTSD) in asylum seekers and refugees are scarce. The aim of this study was to evaluate the effectiveness of three different trauma-focused day-treatment group programs for treatment of PTSD in male asylum seekers and refugees. Three treatment groups (n = 56) and a waitlisted control group (n = 16) of help-seeking Iranian and Afghani patients were assessed with a set of self-rated symptom checklists for PTSD, anxiety, depression, and psychoticism 1 week before and 2 weeks after treatment. There are no indications that the 2 days' group program with three nonverbal and two group psychotherapy sessions per week is less effective in reducing symptoms than the program with the same amount of sessions spread over 3 days per week. The trauma-focused day-treatment group seems a promising approach for treatment of PTSD among asylum seekers and refugees in industrialized settings. Language: en

IntroductionFive to 8% of women of reproductive age suffer from moderate to severe symptoms of premenstrual syndrome associated with substantial distress or functional impairment.ObjectiveTo determine the efficacy, tolerability and acceptability of Vitex agnus castus (VAC, chaste-berry) preparations for treatment of premenstrual syndrome (PMS).MethodsAfter an extensive literature search all randomized controlled trials of VAC in women with PMS and/or premenstrual dysphoric disorder were included.ResultsWe found 17 randomized controlled trials of VAC in the treatment of PMS of which 14 studies could be included in the quantitative analysis. All trials, except one, found the Vitex agnus castus preparation to be more efficacious than placebo, pyridoxine and magnesium for either total symptom score or individual symptoms or symptom clusters. Unfortunately, the majority of trials is hampered by a high risk of bias. The pooled effect of VAC in placebo-controlled trials was large (Hedge's g: −1.21; 95% CI: −1.53 to −0.88), but heterogeneity extremely high (I2 = 91%). We could not single out distinct factors that could explain this heterogeneity. The funnel plot and Egger's tests suggest the presence of bias over the full set of studies and effect sizes.ConclusionAlthough meta-analysis shows a large pooled effect of VAC in placebo-controlled trials the high risk of bias, high heterogeneity and risk of publication bias of the included studies preclude a definitive conclusion. The pooled treatment effects should be viewed as merely explorative and, at best, overestimating the real treatment effect of VAC for PMS symptomatology.Disclosure of interestP.S. reports personal fees from H. Lundbeck A/S, outside the submitted work. The other authors have not supplied their declaration of competing interest.

Importance Compulsory admissions, defined as admissions against the will of the patient (according to local judicial procedures), have a strong effect on psychiatric patients. In several Western countries, the rate of such admissions is tending to rise. Its reduction is urgently needed. Objective To establish which interventions effectively reduce compulsory admissions in adult psychiatric patients in outpatient settings. Data Sources A systematic computerized literature search was performed using EMBASE, MEDLINE, Web of Science, PsycINFO, CINAHL, PubMed (not yet indexed for MEDLINE), Cochrane Central, and Google Scholar. Every database was searched from its inception until April 30, 2015. Study Selection Randomized clinical trials (RCTs) that studied any kind of intervention designed to reduce compulsory admission rates in adult psychiatric patients (age range, 18-65 years) in outpatient settings were eligible. Eligibility was independently assessed by 2 of us. Data Extraction and Synthesis Two of us independently extracted relevant data. The Cochrane Collaboration’s tool was used for assessing risk of bias. Overall risk reduction (random-effects estimate) was calculated in the following 4 subgroups of interventions: advance statements, community treatment orders, compliance enhancement, and integrated treatment. Main Outcomes and Measures Relative risk (RR) was calculated on the basis of the number of patients who had been compulsorily admitted. Results Our meta-analyses included 13 RCTs comprising 2970 psychiatric patients. The meta-analysis of the RCTs on advance statements showed a significant 23% (RR, 0.77; 95% CI, 0.60-0.98; I2 = 2.2%) (n = 1102) risk reduction in compulsory admissions. In contrast, the RCTs on community treatment orders (RR, 0.95; 95% CI, 0.81-1.10; I2 = 0.0%) (n = 742), compliance enhancement (RR, 0.52; 95% CI, 0.11-2.37; I2 = 55.7%) (n = 250), and integrated treatment (RR, 0.71; 95% CI, 0.49-1.02; I2 = 49.0%) (n = 876) showed no significant risk reduction in compulsory admissions. Conclusions and Relevance The meta-analysis of the RCTs on advance statements showed a statistically significant and clinically relevant 23% reduction in compulsory admissions in adult psychiatric patients, whereas the meta-analyses of the RCTs on community treatment orders, compliance enhancement, and integrated treatment showed no evidence of such a reduction. To date, only 13 RCTs have used compulsory admissions as their primary or secondary outcome measure. This demonstrates the need for more research in this field.

Electroconvulsive therapy (ECT) is considered an effective treatment for major depression with melancholic features. However, neurocognitive side-effects such as anterograde amnesia still regularly occur. The present study aims to evaluate the severity and course of anterograde amnesia in severely depressed patients undergoing ECT. In a prospective naturalistic study, anterograde memory function was assessed among inpatients who underwent ECT (n = 11). Subjects met DSM-IV criteria for major depressive disorder. Recruitment took place between March 2010-March 2011 and March 2012-March 2013. Controls treated with antidepressants (n = 9) were matched for age, gender and depression severity. Primary outcome measure was immediate recall; secondary outcome measures were delayed recall, recognition, and visual association. Differences were tested using repeated measures ANOVA and paired t-tests. Correlations with hypothesized covariates were calculated. In patients with major depressive disorder, ECT had a significant effect on delayed memory function (p

Objective: Crisis plans are a type of psychiatric advance statement (PAS) that describe how to recognize early signs of a psychiatric crisis and how to handle crisis situations. Although PASs may help reduce the occurrence of crises, their implementation in clinical practice is problematic. This study examined patient and clinician characteristics associated with successful completion of a crisis plan and determined how often a plan was consulted in a crisis situation. Methods: Participants were 139 crisis-prone outpatients and their clinicians recruited in the context of a randomized controlled trial in the Netherlands studying the effects of crisis plans. Multivariate logistic regression analyses examined associations between patient and clinician characteristics and completion of a crisis plan. Descriptive and univariate statistics were used to determine subsequent use of crisis plans. Results: Of the 139 patients, 64% completed a crisis plan. Higher completion rates were associated with a better clinician-rated working alliance, a lower education level of the patient, and fewer years of professional experience of the clinician. Of the 89 patients who completed a crisis plan, 38 later experienced a crisis, and plans were consulted for a third of these patients (34%). For those whose crisis involved involuntary admission, a smaller proportion had their plans consulted, compared with those whose crisis involved an outpatient emergency visit or voluntary admission. Conclusions: PAS completion was associated not only with patient and clinician characteristics but also with a positive working alliance. PAS use did not occur in all cases, especially not when patients were involuntarily admitted.

Background: Maladaptive emotional control is a defining feature of personality disorders. Yet little is known about the underlying physiological dynamics of emotional reactivity to psychosocial stress across distinct personality disorders. The current study compared subjective emotional responses with autonomic nervous system and HPA axis physiological responses to psychosocial stress in women with cluster C personality disorder (CPD) and borderline personality disorder (BPD). Methods: Subjective mood ratings, salivary cortisol, heart rate (HR), and skin conductance level (SCL) were assessed before, during, and after exposure to a standardized psychosocial stress paradigm (Trier Social Stress Test, TSST) in 26 women with BPD, 20 women with CPD, and 35 healthy female controls. Subjects were free of any medication including hormonal contraceptives, had a regular menstrual cycle, and were tested during the luteal phase of their menstrual cycle. Results: Both CPD and BPD patients reported a similar burden of subjective mood disturbance. However, only BPD patients demonstrated reduced baseline cortisol levels with a blunted cortisol and HR reactivity to the TSST. In addition, BPD patients exhibited a generalized increase of SCL. No significant differences in baseline or TSST reactivity of cortisol, HR, or SCL were observed between CPD patients and healthy controls. Conclusion: These findings indicate that patients with BPD have significant alterations in their physiological stress reactivity, which is notably distinct from patients with CPD and those of healthy controls. (C) 2016 Elsevier Ltd. All rights reserved.