Dose response relationship between lithium serum levels during pregnancy and birth outcomes.

INTRODUCTION: Lithium use during pregnancy reduces the risk of mood episodes in the perinatal period for women with bipolar disorder. Some previous studies found deleterious effects of intrauterine lithium exposure on birth outcomes, yet little is known about a dose response relationship. The current study investigated the influence of maternal lithium serum levels on birth outcomes. METHODS: This retrospective observational cohort study included women with a bipolar spectrum disorder who were referred to a specialized psychiatric and obstetric outpatient clinic from 2003 to 2019 and used lithium during the entire pregnancy. For 101 pregnancies at least one lithium level during pregnancy was available. A weighted average lithium level was calculated for the entire pregnancy, as well as for each trimester. Detailed information on maternal, obstetric and neonatal outcomes were retrieved from the medical records. Linear and logistic regression models were used to investigate the association between weighted average lithium level and pregnancy duration, birth weight percentiles, preterm birth and large for gestational age births (LGA). In subsequent exploratory analyses, we studied the role of thyroid-stimulating hormone (TSH) and thyroxine (T4) as a mediator in the found associations. RESULTS: The weighted average lithium serum level during pregnancy was negatively associated with pregnancy duration and positively with preterm birth, but not with birth weight percentile or LGA. In exploratory analyses, TSH and T4 did not mediate the association between average lithium serum level and pregnancy duration. CONCLUSION: The results of this cohort study during pregnancy indicate a dose response relationship between maternal lithium serum levels and pregnancy duration.

Brain development after intrauterine exposure to lithium: A magnetic resonance imaging study in school-age children.

OBJECTIVE: Lithium is often continued during pregnancy to reduce the risk of perinatal mood episodes for women with bipolar disorder. However, little is known about the effect of intrauterine lithium exposure on brain development. The aim of this study was to investigate brain structure in children after intrauterine exposure to lithium. METHODS: Participants were offspring, aged 8-14 years, of women with a diagnosis of bipolar spectrum disorder. In total, 63 children participated in the study: 30 with and 33 without intrauterine exposure to lithium. Global brain volume outcomes and white matter integrity were assessed using structural MRI and diffusion tensor imaging, respectively. Primary outcomes were total brain, cortical and subcortical gray matter, cortical white matter, lateral ventricles, cerebellum, hippocampus and amygdala volumes, cortical thickness, cortical surface area and global fractional anisotropy, and mean diffusivity. To assess how our data compared to the general population, global brain volumes were compared to data from the Generation R study (N = 3243). RESULTS: In our primary analyses, we found no statistically significant associations between intrauterine exposure to lithium and structural brain measures. There was a non-significant trend toward reduced subcortical gray matter volume. Compared to the general population, lithium-exposed children showed reduced subcortical gray and cortical white matter volumes. CONCLUSION: We found no differences in brain structure between lithium-exposed and non-lithium-exposed children aged 8-14 years following correction for multiple testing. While a rare population to study, future and likely multi-site studies with larger datasets are required to validate and extend these initial findings.

Clinical characteristics associated with relapse 2 years after electroconvulsive therapy for major depression.

OBJECTIVE: High relapse rates are observed after electroconvulsive therapy (ECT) for major depression. Identifying patients who are at increased risk for relapse to intensify their treatment regimen post-ECT might reduce relapse rates. We aimed to determine clinical characteristics that are associated with relapse within 2 years after successful ECT. METHODS: Patients who remitted to ECT in a randomised controlled trial comparing adjuvant nortriptyline and placebo during a course of bilateral ECT were followed-up prospectively for 1 year with open-label nortriptyline (Dutch Trial Register NTR5579). Second-year follow-up data were collected retrospectively. Thirty-four patients were included in this follow-up cohort. To examine the association between clinical characteristics and the risk of relapse, unadjusted hazard ratios (HRs) were calculated. RESULTS: At 2 years post-ECT, the overall relapse rate was 50%, and the HRs for relapse in patients with psychotic features, a higher severity of depression, and medication resistance prior to ECT were 0.33 (CI 0.12-0.89; p = 0.029), 0.88 (CI 0.80-0.98; p = 0.014), and 4.48 (CI 1.28-15.73, p = 0.019), respectively. No effect was found for age, sex or episode duration on the relapse rate. CONCLUSIONS: Depressed patients with psychotic features, with higher symptom severity and without medication resistance prior to ECT have a significantly decreased risk of relapse after successful ECT. A sustained remission rate of 50% over 2 years in patients with severe major depression who were treated with nortriptyline monotherapy after successful ECT is encouraging.

Neurodevelopment in school-aged children after intrauterine exposure to antipsychotics.

OBJECTIVE: Antipsychotics are increasingly prescribed in pregnancy, yet little is known about potential long-term developmental effects on children. In this study, we investigated the effect of prenatal antipsychotic exposure on neurodevelopmental functioning in school-aged children. METHODS: We performed a cross-sectional neurodevelopmental assessment of 91 children aged 6-14 years whose mothers had severe mental illness and were either exposed or unexposed to antipsychotic medication during pregnancy. Neurodevelopmental outcomes were assessed using validated neurodevelopmental assessment instruments to examine the child's IQ and global cognitive functioning, and the presence of any psychiatric disorders and/or learning problems in the child was assessed by parental report. RESULTS: No statistically significant associations were found between antipsychotic exposure during pregnancy and either adverse neurodevelopmental outcomes (IQ, neuropsychological function), likelihood of psychiatric diagnosis, or learning problems based on parental report. Analyses were likely limited in power to detect subtler differences in neurodevelopmental functioning because of small sample size and heterogeneity of the sample. CONCLUSIONS: In this exploratory cohort study, intrauterine exposure to antipsychotics was not associated with any adverse effect on IQ or neurodevelopmental functioning in a cohort of school-aged children (6-14 years).

Timing and type of adverse life events: Impact on substance use among high-risk adolescents.

A robust association has been reported between childhood adverse life events (ALEs) and risky substance use in adolescence. It remains unclear, however, what the impact of type and timing of these ALEs is. We investigated the association between ALEs and substance use in adolescents. ALEs were operationalized as broad (e.g., moving, parental divorce, family sickness) or physically threatening (physical and/or sexual abuse). First, we examined lifetime ALEs, followed by an investigation into their timing. The sample consisted of 909 adolescents (aged 12-18 years) from a cohort oversampled on high levels of emotional and behavioral problems. The primary caregiver indicated which ALEs each adolescent experienced across their lifetime. Adolescents self-reported on number and frequency of substances used. Poisson and ordinal regression models were used to model the associations. The associations between lifetime ALEs and a substance used were observed only for physical ALEs (incidence rate ratio 1.18 [1.03, 1.35], p = 0.02). When investigating timing, physical ALEs after the age of 12 predicted number of substances used (IRR 1.36 [1.13, 1.63], p < .001). Recent ALEs (occurring after age 12) seem to have considerable impact on substance use. Alcohol and drugs as a coping mechanism were considered a plausible explanation for the results.

Fidelity and Clinical Competence in Providing Illness Management and Recovery: An Explorative Study.

Illness Management and Recovery (IMR) is a psychosocial intervention supporting people with serious mental illnesses. In this study, 15 IMR groups were assessed for fidelity and clinician competency to establish the implementation level of all IMR elements and explore complementarity of the IMR Treatment Integrity Scale (IT-IS) to the standard IMR Fidelity Scale. Use of the IT-IS was adapted, similar to the IMR Fidelity Scale. Descriptive statistics were applied. Implementation success of IMR elements varied widely on the IMR Fidelity Scale and IT-IS (M = 3.94, SD = 1.13, and M = 3.29, SD = 1.05, respectively). Twelve IMR elements (60%) were well-implemented, whereas eight (40%) were implemented insufficiently, including some critical cognitive-behavioral techniques (e.g., role-playing). The scales appeared largely complementary, though strongly correlated (r (13) = 0.74, p = 0.002). Providing all IMR elements adequately requires a variety of clinical skills. Specific additional training and supervision may be necessary.

The effect of prenatal lithium exposure on the neuropsychological development of the child.

OBJECTIVES: Lithium is an effective treatment for bipolar disorder, also during pregnancy to prevent the recurrence of episodes in the perinatal period. Little is known about the neuropsychological development of lithium-exposed offspring. The current study was designed to investigate neuropsychological functioning in lithium-exposed children with the aim to provide further knowledge on the long-term effects of lithium use during pregnancy. METHODS: Participants were offspring of women with a diagnosis of bipolar spectrum disorder, aged 6-14 years. In total, 99 children participated in the study, 56 were exposed to lithium in utero and 43 were not exposed to lithium. Neuropsychological tests were administered, including the Snijders-Oomen Nonverbal Intelligence Test and the NEPSY-II-NL assessment. Linear and negative binomial regression models were used to investigate the association between prenatal lithium exposure and neuropsychological functioning. In secondary analyses, the association between lithium blood level during pregnancy and neuropsychological functioning was assessed. Additionally, norm scores and percentiles for task outcomes were calculated. RESULTS: Lithium use during pregnancy was associated with the total number of mistakes made on the Auditory Attention task, but not statistically significant after full adjustment for potential confounding factors. No association between prenatal lithium exposure and IQ was found. Also, no relationship between lithium blood level during pregnancy and neuropsychological functioning was found after adjustment for potential confounders. Task outcomes in both groups were comparable to the general population. CONCLUSION: In this study, we found no evidence for significantly altered neuropsychological functioning of lithium-exposed children at the age of 6-14 years, when compared to non-lithium-exposed controls.

Influence of adjuvant nortriptyline on the efficacy of electroconvulsive therapy: A randomized controlled trial and 1-year follow-up.

OBJECTIVE: There is limited evidence that adding an antidepressant to electroconvulsive therapy (ECT), compared with ECT monotherapy, improves outcomes. We aimed to determine whether the addition of nortriptyline to ECT enhances its efficacy and prevents post-ECT relapse. METHODS: We conducted a randomized, double-blind, placebo-controlled trial (RCT). Patients with major depressive disorder and an indication for ECT received either nortriptyline or placebo during a bilateral ECT course. Outcome measures were mean decrease in Hamilton Rating Scale for Depression (HRSD) score, response, remission, and time to response and remission. Patients who attained remission participated in a 1-year follow-up study with open-label nortriptyline. Outcome measures were relapse and time to relapse. RESULTS: We included 47 patients in the RCT. In the nortriptyline group, 83% showed response, 74% attained remission, and the mean decrease in HRSD score was 21.6 points. In the placebo group these figures were, respectively, 81% (p = 0.945), 73% (p = 0.928) and 20.7 points (p = 0.748). Thirty-one patients participated in the follow-up study. In patients who had received nortriptyline during the RCT, 47% relapsed at a mean of 34.2 weeks. Patients who had received placebo showed similar treatment results. In both study phases, no statistically significant differences between the nortriptyline and the placebo group were found. CONCLUSION: In our sample of severely depressed patients who were often medication resistant and suffering from psychotic depression, the addition of nortriptyline to ECT did not enhance its efficacy or prevent post-ECT relapse. Encouragingly, even in these patients ECT was highly effective and relapse rates were relatively low.

Influence of an adjuvant antidepressant on the efficacy of electroconvulsive therapy: A systematic review and meta-analysis.

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.

T-cell defects and postpartum depression.

BACKGROUND: Most studies of immune dysregulation in perinatal mood and anxiety disorders have focused on peripheral cytokines, but literature from non-perinatal mood disorders also implicates T-cell defects. We sought to characterize proportions of T-cell subtypes in women with postpartum depression. MATERIALS AND METHODS: We enrolled 21 women with postpartum depression (PPD), 39 healthy postpartum controls, and 114 healthy non-postpartum women. Blood was collected in sodium-heparin EDTA tubes and was analyzed using flow cytometry. We conducted statistical tests including linear regression analysis that were aimed at determining differences in proportions of T cell populations among groups. RESULTS: Mean counts of T-cells (all CD3+ T cells), T-helper cells, (CD3+CD4+ T cells), and T-cytotoxic cells (CD3+CD8+ T cells) were significantly increased in healthy postpartum women compared to healthy non-postpartum controls (p < 0.001, p = 0.007, and p = 0.002, respectively), but not in women with PPD. The increases in healthy postpartum women were driven by increases in TH1 cells and T regulatory cells, increases that were nonexistent or attenuated in women with postpartum depression. Mean counts of CD4+ T-helper memory cells were also increased in healthy postpartum women (p = 0.009), but slightly decreased in women with PPD (p = 0.066), when compared to healthy non-postpartum controls. CONCLUSIONS: Our study confirms that the postpartum period in healthy women is a time of enhanced T cell activity. Women with postpartum depression failed to show physiological enhanced T-cell activity postpartum, and future research is needed to elucidate etiological mechanisms and consequences.

Gastrointestinal Symptoms in Infants of Mothers With a Psychiatric History and the Role of Depression and Bonding.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Maternal psychiatric history is associated with infant gastrointestinal symptoms, in which mother-infant bonding is a mediating factor.

Employment Rates in Flexible Assertive Community Treatment Teams in The Netherlands: An Observational Study.

We determined the proportions of clients treated in Flexible Assertive Community Treatment teams who were unemployed and gained employment and who were employed and lost employment. Secondly, we explored the demographical and clinical factors associated with employment. Data were collected during routine outcome monitoring. We calculated differences in employment rates over a year and explored differences in demographic characteristics at baseline between patient groups. Logistic regression analysis was used to estimate the role of clinical predictor variables on employment status. Over time, 10% remained employed, 5% lost their employment, 3% gained employment and 82% remained unemployed. Clients who found employment were younger, more often male, and had significantly fewer psychosocial problems and a higher subjective quality of life during follow-up than those who remained unemployed. Problems with motivation for treatment at baseline were related to losing employment or remaining unemployed. Better implementation of vocational services is very important for increasing the number of clients gaining employment.

Prediction of electroconvulsive therapy response and remission in major depression: meta-analysis.

BACKGROUND: Electroconvulsive 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. Aims To investigate the predictive value of age, depression severity, psychotic and melancholic features for ECT response and remission in major depression. METHOD: A 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. RESULTS: Of 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. CONCLUSIONS: ECT 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 interest None.

Prediction of Electroconvulsive Therapy Response and Remission in Major Depression: Meta-analysis - CORRIGENDUM.

This notice describes a correction to the above mentioned paper.

Guidelines on treatment of perinatal depression with antidepressants: An international review.

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.

Long-term neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics: a systematic review and meta-analysis.

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.

Phenotypical characteristics of postpartum psychosis: A clinical cohort study.

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.

The treatment of premenstrual syndrome with preparations of Vitex agnus castus: a systematic review and meta-analysis.

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 (I2, 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.

Crucial factors preceding compulsory psychiatric admission: a qualitative patient-record study.

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.

Detection of domestic violence by community mental health teams: a multi-center, cluster randomized controlled trial.

BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: ISRCTN:14115257 . Date of registration: 15th January 2015.