The Syndrome of Irreversible Lithium-Effectuated Neurotoxicity: A Scoping Review.

The Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) is a rare but concerning neurological complication resulting from lithium intoxication. Despite being reported since the 1960s, SILENT remains poorly understood and previous reviews on this topic commonly have been narrative. We therefore conducted a scoping review to assess the nature and scope of the research literature on the long-term neurological sequelae of lithium toxicity and determine the current knowledge of SILENT. A comprehensive and systematic literature search, using the MEDLINE, Embase, and Web of Science databases (from inception to July 2023), was conducted for English and Dutch articles, assessing the long-term neurological sequelae of lithium intoxication. Key information concerning clinical manifestations, risk factors, therapeutic approaches, or preventive measurements was extracted. We reviewed 91 articles, extracting information from 117 cases of SILENT. The prevailing outcome observed was persistent cerebellar dysfunction (77% of cases), often in combination with other sequelae. Other common sequelae included cognitive problems, parkinsonism, choreoathetosis, tardive dyskinesia, and peripheral neuropathy. The most common (61.4%) acute neurological symptom in the development of SILENT is an altered level of consciousness ranging from confusion to comatose states. Cerebellar sequelae were mentioned in 77% of cases as most common persistent sequelae. Antipsychotic use was mentioned in 59% of cases and fever was reported in 37.6% of cases. Scientific knowledge about this phenomenon has not advanced much since its initial reports in the 1960s and 1970s. While the use of lithium has become much more stringent than it had been in years past, and the occurrence of SILENT is rather exceptional, raising awareness about SILENT nevertheless remains crucial to avoid deleterious neurological consequences. Comprehensive, high-quality research in a systematic and standardized manner is therefore urgently needed to better understand this phenomenon.

Evaluating Monitoring Guidelines of Clozapine-Induced Adverse Effects: a Systematic Review.

BACKGROUND AND OBJECTIVES: Despite the evidence that no other antipsychotic is effective as clozapine for the treatment of resistant schizophrenia, it is associated with various metabolic, neuroendocrine, cardiovascular, and gastrointestinal adverse effects. Guidelines aiming to address the monitoring of clozapine's (serious) adverse effects can be helpful to prevent and treat these effects. However, many of these guidelines seem to lack one or more important monitoring recommendations. We aimed to systematically review the content and quality of existing monitoring guidelines/recommendations for clozapine-induced adverse effects. METHODS: A comprehensive and systematic literature search, using the MEDLINE, Embase, Web of Science, and Cochrane databases, was conducted for guidelines/recommendations on the monitoring of clozapine-induced adverse events, published between January 2004 and April 2023 (last search 16 April 2023). Only peer-reviewed published guidelines reporting on the comprehensive monitoring of all major clozapine-induced adverse effects and including evidence-based recommendations, developed after the year 2004, were included. Studies reporting on the monitoring of adverse effects of clozapine without being a formal guideline, guidelines reporting on the monitoring of one or a limited number of adverse effects of clozapine, guidelines that were not peer reviewed or published, expert opinion papers without formal consensus guideline development, or guidelines developed before the year 2004, were excluded. The Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool was used to evaluate the guidelines/recommendations' quality. RESULTS: Only one guideline met the inclusion criteria. This consensus statement made recommendations for hematological monitoring, and the monitoring of metabolic, cardiac, and three other adverse effects. Highest scores for the qualitative assessment were found for the domains "scope and purpose" (66.7%), "clarity of presentation" (44.4%), and "editorial independence" (66.7%). Lowest scores were found for "rigor of development" (14.6%) and "applicability" (0%). CONCLUSIONS: Future guidelines should develop more comprehensive recommendations about specific clozapine-induced adverse effects, including constipation, myocarditis, tachycardia, and seizures, as well as include a rechallenge policy. There is an urgent need for well-developed, methodologically stringent, guidelines. REGISTRATION: PROSPERO registration number, CRD42023402480.

Depression and post-traumatic stress disorder after perinatal loss in fathers: A systematic review.

BACKGROUND: Research indicates that perinatal loss can cause profound psychological consequences in parents. However, a comprehensive summary of existing quantitative literature describing the association between perinatal loss and the development of depression/depressive symptoms or post-traumatic stress disorder (PTSD)/post-traumatic stress (PTS) symptoms in fathers has not been published. METHODS: A systematic literature search (from inception to December 2021), using the PubMed, EMBASE, and Web of Science databases to articles assessing depressive or PTS symptoms, was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Only studies investigating the period of intrauterine death from 20 weeks of gestation, stillbirth, or neonatal death within the first month after birth were included. RESULTS: A final sample of 13 articles were eligible for inclusion. Some studies showed an increased risk of depressive and PTS symptoms in fathers after perinatal loss. However, many study results did not show significant differences, symptoms generally decreased over time, and the majority of studies showed higher levels of depressive and PTS symptoms in mothers, compared with fathers. CONCLUSIONS: Although the majority of the included studies showed elevated levels of depressive and/or PTSD symptoms after perinatal loss in fathers, no clear firm conclusion can be drawn, as the included studies were very heterogeneous. More homogeneous research measuring depressive and PTS symptoms in fathers is needed at the time of the loss, as the current literature available shows several limitations and gaps.

Severe Mental Illness and Cardiovascular Disease: JACC State-of-the-Art Review.

People with severe mental illness, consisting of schizophrenia, bipolar disorder, and major depression, have a high burden of modifiable cardiovascular risk behaviors and conditions and have a cardiovascular mortality rate twice that of the general population. People with acute and chronic cardiovascular disease are at a higher risk of developing mental health symptoms and disease. There is emerging evidence for shared etiological factors between severe mental illness and cardiovascular disease that includes biological, genetic, and behavioral mechanisms. This state-of-the art review will describe the relationship between severe mental illness and cardiovascular disease, explore the factors that lead to poor cardiovascular outcomes in people with severe mental illness, propose strategies to improve the cardiovascular health of people with severe mental illness, and present areas for future research focus.

Media coverage of Belgium's first criminal case concerning euthanasia for psychiatric patients: A content analysis of Flemish newspapers and magazines.

Background: Belgium is one of the few countries worldwide where euthanasia on the grounds of unbearable suffering caused by a psychiatric disorder is legally possible. In April 2010 euthanasia was carried out on a 38-year-old Belgian woman with borderline personality disorder and/or autism. After a complaint by the family, three physicians were referred to the Court of Assizes on the charge of "murder by poisoning". Methods: A content analysis of print and online news coverage of the euthanasia case in a selected sample of Flemish newspapers and magazines, published between December 1, 2019 and March 1, 2020, was conducted to analyze the prominence and framing of the euthanasia case, as well as the portrayal of key figures in this case. A quantitative analysis, as well as an in-depth qualitative analysis (with the aid of NVivo 1.0 software) was performed. Results: One thousand two hundred fifteen news articles were identified through database searching. Of these, 789 articles were included after screening for relevance and eligibility. Mean prominence scores were moderate and did not statistically significantly differ between newspapers with a different historical ideological background or form (elite versus popular). The most frequent headline topics featured legal aspects (relating to the Belgian Euthanasia Law or the course of the trial). Headlines and content of most articles (90 and 89%, respectively) did not contain an essential standpoint on the euthanasia case itself or, if they did, were neutral. Historical ideological background, nor form of newspaper (elite versus popular) significantly influenced headline tone or article direction toward the euthanasia case. Despite this, our qualitative analysis showed some subtle differences in selection, statement or tonality of reports between certain newspapers with a different historical ideological background. Conclusion: Although major Flemish newspapers and magazines generally were neutral in their coverage of the judicial case, major points of contention discussed were: the need for an evaluation and possible amendments to the existing Euthanasia Law, including a revision of the Belgian Control Commission and the system of penalties for physicians, and the absence of any consensus or guidance on how to define psychological suffering.

COVID-19 vaccination for people with severe mental illness: why, what, and how?

Psychiatric disorders, and especially severe mental illness, are associated with an increased risk of severe acute respiratory syndrome coronavirus 2 infection and COVID-19-related morbidity and mortality. People with severe mental illness should therefore be prioritised in vaccine allocation strategies. Here, we discuss the risk for worse COVID-19 outcomes in this vulnerable group, the effect of severe mental illness and psychotropic medications on vaccination response, the attitudes of people with severe mental illness towards vaccination, and, the potential barriers to, and possible solutions for, an efficient vaccination programme in this population.

Does lithium prevent relapse following successful electroconvulsive therapy for major depression? A systematic review and meta-analysis.

OBJECTIVE: The risk of relapse following successful antidepressant treatment, including electroconvulsive therapy (ECT), is substantial. Lithium has been suggested to effectively prevent relapse, yet data remain limited and inconclusive. We performed a systematic review and meta-analysis to examine the efficacy of continuation treatment with lithium in preventing relapse following a successful acute course of ECT in patients with major depression, in comparison to continuation treatment without lithium. We also assessed the role of several study characteristics, possibly impacting the treatment effect. METHODS: A systematic literature search, using the PubMed, Embase, Web of Science, and Cochrane Library databases (up to June 2020), was conducted for prospective and retrospective studies, including patients with unipolar or bipolar depression, that assessed the efficacy of lithium for post-ECT depressive relapse prevention. RESULTS: Of 2556 records screened, 14 articles reporting on 9748 participants who received continuation treatment either with (N = 1571) or without lithium (N = 8177) were included in the meta-analysis. Patients receiving lithium were less likely to experience depressive relapse after a successful acute course of ECT, compared to patients receiving post-ECT prophylaxis without lithium (weighted odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.34, 0.82), with a number needed to treat (NNT) of 7 (95% CI = 4, 21). We found some limited evidence that older patients may benefit more from continuation treatment with lithium, compared to younger patients. Using the GRADE criteria, the quality of evidence for our outcome measure (i.e., relapse rate) was rated as very low. CONCLUSION: Continuation treatment with lithium may have superior efficacy in reducing the risk of relapse after a successful acute ECT course for major depression, in comparison to continuation treatment without lithium. High-quality studies are needed to confirm this finding.

COVID-19 Vaccination Rates in a Cohort Study of Patients With Mental Illness in Residential and Community Care.

Background: Patients with mental illness are at increased risk for COVID-19-related morbidity and mortality. Vaccination against COVID-19 is important to prevent or mitigate these negative consequences. However, concerns have been raised over vaccination rates in these patients. Methods: We retrospectively examined vaccine uptake in a large sample of Belgian patients admitted to or residing in a university psychiatric hospital or community mental health care setting between 29th of March 2021 and 30th of September 2021 in the Flanders Region. All patients were offered vaccination. Descriptive statistics were used to analyse the data. Logistic regression was used to examine factors associated with vaccine uptake. Results: 2,105 patients were included in the sample, of which 1,931 agreed to be vaccinated, corresponding with a total vaccination rate of 91.7%. Logistic regression showed an effect of the diagnosis "other disorders" (OR = 0.08, CI = 0.005-0.45), age (OR = 1.03, CI = 1.02-1.04) and residing in the psychosocial care center (OR = 0.50, CI = 0.32-0.80) on vaccination status. Conclusion: Vaccine uptake among people with mental illness is high and comparable to the general population, when implementing a targeted vaccination program.

Barriers to Somatic Health Care for Persons With Severe Mental Illness in Belgium: A Qualitative Study of Patients' and Healthcare Professionals' Perspectives.

BACKGROUND: A huge and still growing mortality gap between people with severe mental illness (SMI) and the general population exists. Physical illnesses, mainly cardiovascular diseases, substantially contribute to the high mortality rates in patients with SMI. Disparities in somatic health care access, utilisation, and provision contribute to these poor physical health outcomes. METHODS: A qualitative study, using semi-structured interviews, was set up to explore SMI patients' and healthcare professionals' perspectives on somatic health care in different psychiatric settings of the three Belgian regions (Flanders, Brussels, Wallonia). Interviews were digitally recorded and transcribed prior to qualitative inductive thematic analysis, using Nvivo software. The COnsolidated criteria for REporting Qualitative research (COREQ) were used for reporting methods and findings. RESULTS: Collaboration and information flows between psychiatric healthcare professionals, non-psychiatric healthcare professionals, and persons with SMI were troublesome. This seemed to be mainly due to stigma and prejudice and challenging communication and data transfer. Lack of sufficient training and experience to identify and treat somatic health problems in people with SMI (for psychiatrists and psychiatric nurses) and lack of psychiatric knowledge and feeling or sensitivity for psychiatric patients (for non-psychiatric healthcare professionals) further complicated adequate somatic health care. Finally, optimal somatic follow-up of patients with SMI was hampered by organisational problems (unavailability of equipment, unadapted infrastructure, understaffing, hospital pharmacy issues, and insufficient health promotion/lifestyle interventions), patient-related issues (unawareness of physical problems, non-adherence, need for accompaniment) and financial barriers. CONCLUSION: There is an urgent need for integrated somatic and mental healthcare systems and a cultural change. Psychiatrists and primary care providers continue to consider the mental and physical health of their patients as mutually exclusive responsibilities due to a lack of sufficient training and experience, poor or absent liaison links, time constraints and organisational and financial barriers. Modifying these aspects will improve the quality of somatic health care for these vulnerable patients.

COVID-19-Related Mortality Risk in People With Severe Mental Illness: A Systematic and Critical Review.

Background: Increasing clinical evidence suggests that people with severe mental illness (SMI), including schizophrenia spectrum disorders, bipolar disorder (BD), and major depressive disorder (MDD), are at higher risk of dying from COVID-19. Several systematic reviews examining the association between psychiatric disorders and COVID-19-related mortality have recently been published. Although these reviews have been conducted thoroughly, certain methodological limitations may hinder the accuracy of their research findings. Methods: A systematic literature search, using the PubMed, Embase, Web of Science, and Scopus databases (from inception to July 23, 2021), was conducted for observational studies assessing the risk of death associated with COVID-19 infection in adult patients with pre-existing schizophrenia spectrum disorders, BD, or MDD. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Results: Of 1,446 records screened, 13 articles investigating the rates of death in patients with pre-existing SMI were included in this systematic review. Quality assessment scores of the included studies ranged from moderate to high. Most results seem to indicate that patients with SMI, particularly patients with schizophrenia spectrum disorders, are at significantly higher risk of COVID-19-related mortality, as compared to patients without SMI. However, the extent of the variation in COVID-19-related mortality rates between studies including people with schizophrenia spectrum disorders was large because of a low level of precision of the estimated mortality outcome(s) in certain studies. Most studies on MDD and BD did not include specific information on the mood state or disease severity of patients. Due to a lack of data, it remains unknown to what extent patients with BD are at increased risk of COVID-19-related mortality. A variety of factors are likely to contribute to the increased mortality risk of COVID-19 in these patients. These include male sex, older age, somatic comorbidities (particularly cardiovascular diseases), as well as disease-specific characteristics. Conclusion: Methodological limitations hamper the accuracy of COVID-19-related mortality estimates for the main categories of SMIs. Nevertheless, evidence suggests that SMI is associated with excess COVID-19 mortality. Policy makers therefore must consider these vulnerable individuals as a high-risk group that should be given particular attention. This means that targeted interventions to maximize vaccination uptake among these patients are required to address the higher burden of COVID-19 infection in this already disadvantaged group.

Impact of Psychotropic Medication Effects on Obesity and the Metabolic Syndrome in People With Serious Mental Illness.

People with serious mental illness (SMI), including schizophrenia, bipolar disorder, and major depressive disorder, have a higher mortality rate and shortened life expectancy. This is mainly attributable to physical diseases, particularly cardiovascular diseases (CVDs). Important risk factors for CVDs are obesity and other metabolic abnormalities, which are especially prevalent in people with SMI. Several factors contribute to this increased risk, including unhealthy lifestyles. Psychotropic medication independently further increases this risk. In this review we want to examine the relationship between obesity and other components of the metabolic syndrome and psychotropic medication in people with SMI.

Medication-Induced Akathisia with Newly Approved Antipsychotics in Patients with a Severe Mental Illness: A Systematic Review and Meta-Analysis.

BACKGROUND: Akathisia is a common and distressing movement disorder that can be associated with the use of antipsychotics. It is characterized by a subjective (inner restlessness) and an objective (excessive movements) component. Akathisia can have a negative impact on clinical outcome and even lead to treatment discontinuation. Although medication-induced akathisia is more commonly associated with the use of first-generation antipsychotics (FGAs), it also occurs with second-generation antipsychotics (SGAs), including the newly approved antipsychotics (NAPs) asenapine, lurasidone, iloperidone, cariprazine, and brexpiprazole. Until now, no meta-analysis has been published on the risk of akathisia for all NAPs, as monotherapy or adjunctive treatment, in patients with a severe mental illness. OBJECTIVE: The primary objectives of this systematic review and meta-analysis were to (i) compare akathisia incidence rates of the NAPs, as monotherapy or adjunctive treatment, in adult patients with a severe mental illness (i.e., schizophrenia, bipolar disorder, or major depressive disorder), using data from published and unpublished randomized controlled trials; and (ii) examine the role of several study characteristics explaining differences in akathisia incidence rates between studies. METHODS: A systematic literature search, using the PubMed, EMBASE, and Cochrane Library databases (until October 2018), was conducted for English-language placebo- as well as active-controlled clinical trials, including subjective (percentage of patients reporting akathisia) and/or scale-defined medication-induced akathisia incidence rates with NAPs (as monotherapy or as adjunctive treatment) in adult patients with schizophrenia, bipolar disorder, or major depressive disorder. Additional unpublished clinical trials were identified through the ClinicalTrials.gov electronic database. Two meta-analyses (incidence rates and odds ratio [OR] [placebo vs. active] of medication-induced akathisia with NAPs) were performed to obtain an optimal estimation of akathisia risks of adult patients with a severe mental illness under these treatment conditions and to assess the role of study characteristics. RESULTS: Two hundred and thirteen reports were selected as potentially eligible for our meta-analysis. Of these, 48 met the inclusion criteria. Eight records, identified through the ClinicalTrials.gov database and cross-referencing, and which fulfilled the inclusion criteria, were added, resulting in a total of 56 records (iloperidone = 5, asenapine = 11, lurasidone = 15, brexpiprazole = 13, cariprazine = 12). The estimated weighted mean incidence rate of akathisia was 7.7% (95% confidence interval [CI] 6.5-9.1), with estimates being 3.9% (95% CI 2.4-6.3) for iloperidone, 6.8% (95% CI 5.1-9.0) for asenapine, 10.0% (95% CI 7.4-13.5) for brexpiprazole, 12.7% (95% CI 10.1-16.1) for lurasidone, and 17.2% (95% CI 13.4-22.1) for cariprazine. After Tukey-adjustment for multiple testing, the incidence rate of akathisia was significantly (p < 0.05) lower for iloperidone than for brexpiprazole, lurasidone, and cariprazine. In addition, the incidence rate of akathisia was significantly (p < 0.05) lower for asenapine than for lurasidone and cariprazine. Finally, the incidence rate of akathisia was significantly (p < 0.05) lower for brexpiprazole than for cariprazine. Type of medication (p < 0.0001), diagnosis (p = 0.02), and race (p = 0.0003) significantly explained part of the heterogeneity of the incidence estimates of akathisia between studies. The estimated weighted OR of akathisia under medication, compared with placebo, was 2.43 (95% CI 1.91-3.10). The OR was smallest for iloperidone (OR 1.20; 95% CI 0.42-3.45) and increased for brexpiprazole (OR 2.04; 95% CI 1.09-3.83), asenapine (OR 2.37; 95% CI 1.32-4.27), lurasidone (OR 3.74; 95% CI 2.32-6.02), and cariprazine (OR 4.35; 95% CI 2.80-6.75). Only type of medication (p = 0.03) explained systematic differences in the OR for akathisia between placebo versus active treatment across studies. After Tukey-adjustment for multiple testing, no significant differences between these ORs were found. The severity of akathisia with NAPs generally is mild to moderate, only leading to treatment discontinuation in a minority of cases (< 5%). CONCLUSIONS: The use of a NAP raises the akathisia risk more than two-fold when compared with patients receiving placebo. Although distinctions between the different NAPs were not clear in placebo-controlled trials, the results of our meta-analyses and systematic review generally indicate that these differences more than likely reflect real differences, with iloperidone showing the most and cariprazine showing the least benign akathisia profile. Moreover, due to patient characteristics and methodological issues, incidence rates of akathisia with NAPs found in this meta-analysis may even be an underestimation of true incidence rates.

The intriguing relationship between coronary heart disease and mental disorders.

Coronary heart disease (CHD) and mental illness are among the leading causes of morbidity and mortality worldwide. Decades of research has revealed several, and sometimes surprising, links between CHD and mental illness, and has even suggested that both may actually cause one another. However, the precise nature of these links has not yet been clearly established. The goal of this paper, therefore, is to comprehensively review and discuss the state-of-the-art nature of the epidemiological and pathophysiological aspects of the bidirectional links between mental illness and CHD. This review demonstrates that there exists a large body of epidemiological prospective data showing that people with severe mental illness, including schizophrenia, bipolar disorder, and major depressive disorder, as a group, have an increased risk of developing CHD, compared with controls [adjusted hazard ratio (adjHR)=1.54; 95% CI: 1.30-1.82, P<0.0001]. Anxiety symptoms or disorders (Relative Risk (RR)=1.41, 95% CI: 1.23-1.61, P<0.0001), as well as experiences of persistent or intense stress or posttraumatic stress disorder (PTSD) (adjHR=1.27, 95% CI: 1.08-1.49), although to a lesser degree, may also be independently associated with an increased risk of developing CHD. On the other hand, research also indicates that these symptoms/mental diseases are common in patients with CHD and may be associated with a substantial increase in cardiovascular morbidity and mortality. Finally, mental diseases and CHD appear to have a shared etiology, including biological, behavioral, psychological, and genetic mechanisms.

La enfermedad coronaria (EC) y los trastornos mentales están entre las principales causas de morbilidad y mortalidad en todo el mundo. Décadas de investigación han revelado varias relaciones, y a veces sorprendentes, entre EC y enfermedad mental e incluso se ha sugerido que ambas pueden ser causa una de la otra. Sin embargo, aún no se ha establecido claramente la naturaleza precisa de estas relaciones. Por lo tanto, el objetivo de este artículo es revisar y discutir de manera comprensible el estado del arte de la naturaleza de los aspectos epidemiológicos y fisiopatológicos de las relaciones bidireccionales entre la enfermedad mental y la EC. Esta revisión demuestra que existe un gran conjunto de datos epidemiológicos prospectivos que encuentran que las personas con enfermedades mentales graves, incluyendo esquizofrenia, trastorno bipolar y trastorno depresivo, como grupo, tienen un riesgo aumentado de desarrollar EC, en comparación con controles [razón de riesgo ajustada (RRa)=1,54; 95% CI: 1,30-1,82; P<0,0001]. Aunque en menor grado, tanto los síntomas ansiosos o trastornos de ansiedad [Riesgo relativo (RR)= 1,41, 95% CI: 1,23-1,61; P<0,0001], como las experiencias de estrés intenso o persistente, o el trastorno por estrés postraumático (TEPT) (RRa=1,27, 95% CI: 1,08-1,49), también pueden estar asociados de manera independiente con un riesgo aumentado de desarrollar EC. Por otra parte, la investigación también indica que estos síntomas o patologías mentales son comunes en pacientes con EC y pueden estar asociadas con un aumento significativo de la morbilidad y mortalidad cardiovascular. Por último, las enfermedades mentales y la EC parecen tener una etiología compartida, incluyendo mecanismos biológicos, conductuales y psicologicos.

La maladie coronaire (MC) et la maladie mentale font partie des principales causes de morbidité et de mortalité dans le monde. Des décennies de recherche ont montré plusieurs liens, parfois surprenants, entre les deux et ont même suggéré qu'en fait, l'un pouvait entraîner l'autre et réciproquement. La nature de ces liens n'est cependant pas claire. Cet article a donc pour but d'analyser de façon exhaustive et de discuter les connaissances épidémiologiques et physiopathologiques les plus récentes concernant les liens bidirectionnels entre la maladie mentale et la MC. Dans cet article, de nombreuses données épidémiologiques prospectives montrent que le risque de développer une MC chez les sujets atteints de maladie mentale sévère comme la schizophrénie, les troubles bipolaires et les troubles dépressifs majeurs, en tant que groupe, est augmenté comparé au risque de sujets témoins (Rapport de risque ajusté HRadj = 1,54 ; IC 95 % ; 1,3-1,82 p<0,0001). Les troubles ou symptômes anxieux (Risque relatif RR = 1,41 ; IC 95 %: 1,23-1,61 p<0,0001) de même que les expériences de stress intense ou persistant ou les troubles de stress post-traumatique (TSPT) (HRadj =1,27 ; IC 95 %: 1,08-1,49), bien qu'a un moindre degré, peuvent aussi être associés de façon indépendante à un risque augmenté de développer une MC. D'un autre côté, d'après la recherche, ces symptômes/troubles mentaux sont courants chez les patients atteints de MC et peuvent s'associer à une morbidité et mortalité cardiovasculaires augmentées de façon importante. Enfin, les troubles mentaux et la MC semblent partager des facteurs étiologiques communs, y compris par des mécanismes biologiques, comportementaux, psychologiques et génétiques.

Antipsychotic treatment, prolactin, and breast tumorigenesis.

BACKGROUND: Over the last decades prolactin (PRL) has gained attention for its possible role in breast tumorigenesis. As all antipsychotics (although differences with respect to PRL elevation are large) have the propensity to induce hyperprolactinemia (HPRL), questions have arisen concerning the influence of PRL-elevating antipsychotic medications on breast cancer risk. SUBJECTS AND METHODS: A literature search (until January 2016), using the MEDLINE database, was conducted for English-language published clinical studies to identify and synthesize data of the current state of knowledge concerning the relationship between HPRL, breast cancer risk (factors) and antipsychotic medication. RESULTS: Results of human prospective studies evaluating the relationship between pre-diagnostic circulating PRL levels and breast cancer risk are limited, equivocal and only correlational. Associations between higher circulating PRL levels and other breast cancer risk factors than nulliparity and hormone therapies mostly have been negative for both pre-and postmenopausal women. Until today, no causal link between (chronic) administration of antipsychotics and breast tumorigenesis in humans has been demonstrated. Finally, several reports describe mechanisms of cancer protection with the PRL hormone as well as with antipsychotic medication. CONCLUSION: The role of PRL in breast carcinogenesis therefore remains unclear, unconfirmed, yet controversial. Antipsychotics should not be withhold for breast cancer prevention reasons to patients in need of this sometimes life-saving medication, even if classical breast cancer risk factors are present.

Relationship between antipsychotic medication, serum prolactin levels and osteoporosis/osteoporotic fractures in patients with schizophrenia: a critical literature review.

INTRODUCTION: Using an antipsychotic medication can increase prolactin (PRL) levels, causing hyperprolactinemia (HPRL). Although the occurrence of osteoporosis within the population of patients with schizophrenia has been recognized, the precise nature of the association between antipsychotic treatment, PRL, osteoporosis, and the disease itself seems to be elusive. AREAS COVERED: The aim of this review is to critically review the literature regarding the association between osteoporosis and PRL and to summarize the available evidence with respect to the impact of PRL-elevating antipsychotics on bone mineral density (BMD) and fractures in non-elderly patients with schizophrenia. EXPERT OPINION: Although long-standing HPRL can have an impact on the rate of bone metabolism and, when associated with hypogonadism, may lead to decreased bone density in both female and male subjects, the relative contribution of antipsychotic-induced HPRL in bone mineral loss in patients with schizophrenia remains unclear. Methodological shortcomings of existing studies, including the lack of prospective data and the focus on measurements of BMD instead of bone turnover markers, preclude definitive conclusions regarding the relationship between PRL-raising antipsychotics and BMD loss in patients with schizophrenia. Therefore, more well conducted prospective trials of these biomarkers are necessary to establish the precise relationship between antipsychotics, PRL levels and osteoporosis/osteoporotic risk.

The Use of Continuous Treatment Versus Placebo or Intermittent Treatment Strategies in Stabilized Patients with Schizophrenia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with First- and Second-Generation Antipsychotics.

BACKGROUND: Although continuous treatment with antipsychotics is still recommended as the gold standard treatment paradigm for all patients with schizophrenia, some clinicians question whether continuous antipsychotic treatment is necessary, or even justified, for every patient with schizophrenia who has been stabilized on antipsychotics. OBJECTIVE: The primary objectives of this systematic review and meta-analysis were (i) to compare relapse/hospitalization risks of stabilized patients with schizophrenia under active versus intermittent or placebo treatment conditions; (ii) to examine the role of several study characteristics, possibly intervening in the relationship between relapse risk and treatment condition; and (iii) to examine whether time to relapse is associated with antipsychotic treatment duration. METHODS: A systematic literature search, using the MEDLINE database (1950 until November 2014), was conducted for English-language published randomized controlled trials, covering a follow-up time period of at least 6 months, and investigating relapse/rehospitalization and/or time-to-relapse rates with placebo or intermittent treatment strategies versus continuous treatment with oral and long-acting injectable first- or second-generation antipsychotics (FGAs/SGAs) in stabilized patients with schizophrenia. Additional studies were identified through searches of reference lists of other identified systematic reviews and Cochrane reports. Two meta-analyses (placebo versus continuous and intermittent versus continuous treatment) were performed to obtain an optimal estimation of the relapse/hospitalization risks of stabilized patients with schizophrenia under these treatment conditions and to assess the role of study characteristics. For time-to-relapse data, a descriptive analysis was performed. RESULTS: Forty-eight reports were selected as potentially eligible for our meta-analysis. Of these, 21 met the inclusion criteria. Twenty-five records, identified through Cochrane and other systematic reviews and fulfilling the inclusion criteria, were added, resulting in a total of 46 records. Stabilized patients with schizophrenia who have been exposed for at least 6 months to intermittent or placebo strategies, respectively, have a 3 (odds ratio [OR] 3.36; 95% CI 2.36-5.45; p < 0.0001) to 6 (OR 5.64; 95% CI 4.47-7.11; p < 0.0001) times increased risk of relapse, compared with patients on continuous treatment. The availability of rescue medication (p = 0.0102) was the only study characteristic explaining systematic differences in the OR for relapse between placebo versus continuous treatment across studies. Studies reporting time-to-relapse data show that the time to (impending) relapse is always significantly delayed with continuous treatment, compared with placebo or intermittent treatment strategies. Although the interval between treatment discontinuation and symptom recurrence can be highly variable, mean time-to-relapse data seem to indicate a failure of clinical stability before 7-14 months with intermittent and before 5 months with placebo treatment strategies. For all reports included in this systematic review, median time-to-relapse rates in the continuous treatment group were not estimable as <50% of the patients in this treatment condition relapsed before the end of the study. CONCLUSIONS: With continuous treatment, patients have a lower risk of relapse and remain relapse free for a longer period of time compared with placebo and intermittent treatment strategies. Moreover, 'success rates' in the intermittent treatment conditions are expected to be an overestimate of actual outcome rates. Therefore, continuous treatment remains the 'gold standard' for good clinical practice, particularly as, until now, only a few and rather general valid predictors for relapse in schizophrenia are known and subsequent relapses may contribute to functional deterioration as well as treatment resistance in patients with schizophrenia.

A systematic review of physical activity correlates in alcohol use disorders.

BACKGROUND: Physical activity might promote mental and physical health in persons with alcohol use disorder. Understanding the barriers and facilitators of participation in physical activity in persons with alcohol use disorder is an essential first step in order to devise effective physical activity interventions. OBJECTIVE: The present review provides a systematic quantitative review of the correlates of physical activity in people with alcohol use disorder. METHODS: Major electronic databases were searched by two independent authors from inception until June 2014. Keywords included 'physical activity' or 'exercise' and 'alcohol dependence' or 'alcohol abuse' or 'alcohol use disorders' or 'alcoholism'. RESULTS: Five papers evaluating 14 correlates were included. Three studies reported that alcohol dependence was unrelated to physical activity behavior, while alcohol abuse showed positive associations in 2 studies. No demographic variable was related with physical activity participation. Functional impairments and distress associated with alcohol use disorders including increased smoking rates, obesity, anxiety, depression and a lower self-efficacy may limit one's ability to be physically active. Data on social, environmental and policy related factors are currently lacking. No included study assessed physical activity levels utilizing objective measurements (e.g. pedometers, accelerometers). CONCLUSION: Although the literature on physical activity correlates in persons with alcohol use disorder still is equivocal, our varied findings support the hypothesis that the participation in physical activity by people with alcohol use disorder is determined by a range of complex factors.