Lifetime sexual violence experienced by women asylum seekers and refugees hosted in high-income countries: Literature review and meta-analysis.

Screening and care for victims of sexual violence (SV) among asylum seekers and refugees (ASRs) living in High-income host countries were prioritized by the WHO in 2020. The lack of stabilized prevalence findings on lifetime SV among ASRs in High-income countries hinders the development of adequate health management. The objective of this study was to determine the lifetime prevalence of SV experienced by ASRs living in High-income countries. We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included in the meta-analysis if the sample consisted exclusively of asylum seekers or refugees over the age of 16 living in High-income countries and if they reported a lifetime prevalence of experienced SV. The results of the meta-analysis were expressed with 95 % confidence intervals (CIs) as estimates of lifetime SV prevalence using a random-effects model. The estimated lifetime prevalence of SV among women ASRs was 44 % (95 % CI, 0.24-0.67) and 27 % (95 % CI, 0.18-0.38) for both sexes. This meta-analysis revealed a high prevalence of SV among ASRs hosted in High-income countries and suggest the importance of developing specific screening and care programs in these host countries.

Sexual Dysfunction in Schizophrenia: A Systematic Review and Meta-Analysis.

Importance: In individuals with schizophrenia, antipsychotic-induced dysfunctions are frequent but often underexplored in clinical practice. Objective: To synthetize the data of observational studies exploring the prevalence of sexual dysfunction in individuals with schizophrenia-spectrum disorders as well as associated factors. Data Sources: A systematic literature search without language or time restrictions was conducted in Google, Google Scholar, PubMed/MEDLINE, Science Direct, and Université Sorbonne Paris Cité for studies published up to June 8, 2022. Study Selection: All observational studies reporting a prevalence of sexual dysfunction in schizophrenia-spectrum disorder were included. Data Extraction and Synthesis: The MOOSE guidelines with independent extraction by 2 observers and random-effects models were used. Main Outcomes and Measures: The prevalence of sexual dysfunction and each specific dysfunction. Results: A total of 72 of 1119 studies from 33 countries on 6 continents published from inception to June 2022 were included with a total of 21 076 participants with schizophrenia. The pooled global prevalence of sexual dysfunctions was 56.4% (95% CI, 50.5-62.2), with a prevalence of 55.7% (95% CI, 48.1-63.1) for men and 60.0% (95% CI, 48.0-70.8) for women. The most frequent sexual dysfunction was erectile dysfunction in men (44%; 95% CI, 33.5-55.2), followed by loss of libido in men (41%; 95% CI, 30.7-51.4), ejaculation dysfunction in men (39%; 95% CI, 26.8-51.8), orgasm dysfunction in women (28%; 95% CI, 18.4-40.2), and amenorrhea in women (25%; 95% CI, 17.3-35.0). Factors associated with heterogeneity were study design, time and location, sociodemographic data, alcohol use disorder, psychiatric diagnosis, illness severity, and the use of antidepressants and anxiolytics. Sexual dysfunctions were more frequent in schizophrenia vs schizoaffective disorders, and erectile disorders were less frequent in individuals with longer illness duration. Antidepressant and mood stabilizer prescriptions were associated with lower rates of erection disorders (ß, -6.30; 95% CI, -10.82 to -1.78); P = .006 and -13.21; 95% CI, -17.59 to -8.83; P < .001, respectively) and ejaculation disorders (ß, -6.10; 95% CI, -10.68 to -1.53; P = .009 and ß, -11.57; 95% CI, -16.34 to -6.80; P < .001, respectively). No obvious improvements in the rates of sexual dysfunction at other times were found, and there were conflicting results regarding antipsychotic classes. Conclusions and Relevance: This systematic review and meta-analysis found a high prevalence of sexual dysfunction among individuals with schizophrenia, with considerable heterogeneity in associated factors. The findings also suggest that some dysfunctions may be explained by schizophrenia. The association between lower rates of dysfunction and antidepressant use suggests that treating comorbid depression could be an effective strategy to improve sexual health. A lack of data on metabolic parameters and physical health in general was also noted, while these issues are frequent in the care of schizophrenia.

Long-term remission following esketamine nasal spray sessions in a patient with severe and highly treatment-resistant depression: a single-case report.

About 30% of patients with major depressive disorder have treatment-resistant depression (TRD). Recently, intranasal esketamine was approved as a treatment option after the failure of two antidepressant trials. We report a patient with multiresistant depression that was successfully and safely treated with esketamine nasal spray. This 31-year-old inpatient with severe, chronic, and multi-TRD received an acute course of intranasal esketamine (84 mg). Previously, 14 different antidepressants, alone or in potentiation, and several neurostimulation techniques had been unsuccessful. Over 20 bi-weekly sessions, she had no significant adverse effects and was stabilized into remission. During the maintenance phase and 1 year after, she continues to be stable. This case report provides an example of a patient with severe TRD that showed significant improvement after treatment with intranasal esketamine.

Virtual reality cue exposure therapy for tobacco relapse prevention: a comparative study with standard intervention.

BACKGROUND: Successful interventions have been developed for smoking cessation although the success of smoking relapse prevention protocols has been limited. Cognitive behavioural therapy (CBT) in particular has been hampered by a high relapse rate. Because relapse can be due to conditions associated with tobacco consumption (such as drinking in bars with friends), virtual reality cue exposure therapy (VRCE) can be a potential tool to generate 3D interactive environments that simulate risk situations for relapse prevention procedures. METHODS: To assess the effectiveness of VRCE with CBT, a comparative trial involving 100 smoking abstinent participants was designed with all required virtual environments (VE) created with an inexpensive graphic engine/game level editor. RESULTS: Outcome measures confirmed the immersive and craving eliciting effect of these VEs. Results demonstrated that more participants in the VRCE group did not experience smoking relapse and that VRCE is at least as efficacious as traditional CBT in terms of craving reduction and decrease in nicotine dependence. Dropout and relapse rate in the VRCE group was noticeably lower than the CBT group. Aside from mood scores, no significant differences were found regarding the other scales. CONCLUSION: The present clinical trial provides evidence that VRCE was effective in preventing smoking relapse. Improvement in technology and methodology for future research and applications is delineated.

ADHD prevalence in patients with hypersexuality and paraphilic disorders: a systematic review and meta-analysis.

Hypersexuality and paraphilic disorders have been associated with increased ADHD in several studies. To determine the prevalence of ADHD in hypersexuality and paraphilic disorders. Three databases (Medline, Web of Science and Google Scholar) were explored. Using random effects models, we calculated the pooled estimate of ADHD prevalence. The leave-1-out method and subgroup analyses were carried out to identify sources of heterogeneity. Seven studies from three countries (N = 730 patients with hypersexuality) were included (including five US studies). The overall estimate of the prevalence of ADHD in patients with hypersexuality or paraphilic disorders was 22.6% (95% interval: 17-29.4) with high heterogeneity (I2 = 63%). No publication bias was observed according to Egger's test. We found no significant difference in ADHD prevalence between the following subgroups: hypersexuality vs. paraphilic disorders, studies exploring the history of childhood ADHD vs. adult ADHD, US studies vs. others. The French study was a source of heterogeneity with a much lower rate than others (4.5%) but did not significantly change the prevalence estimate. Removing this study increases the prevalence to 25%. We found no association between the year of publication and ADHD prevalence. ADHD is much more frequent in populations with hypersexuality or paraphilic disorders compared to the general population. It should be systematically screened. The subgroup analyses were not sufficient to identify all sources of heterogeneity, other sources should be explored in further studies.

Towards Precision Dosing of Clozapine in Schizophrenia: External Evaluation of Population Pharmacokinetic Models and Bayesian Forecasting.

BACKGROUND: Therapeutic drug monitoring and treatment optimization of clozapine are recommended, owing to its narrow therapeutic range and pharmacokinetic (PK) variability. This study aims to assess the clinical applicability of published population PK models by testing their predictive performance in an external data set and to determine the effectiveness of Bayesian forecasting (BF) for clozapine treatment optimization. METHODS: Available models of clozapine were identified, and their predictive performance was determined using an external data set (53 patients, 151 samples). The median prediction error (PE) and median absolute PE were used to assess bias and inaccuracy. The potential factors influencing model predictability were also investigated. The final concentration was reestimated for all patients using covariates or previously observed concentrations. RESULTS: The 7 included models presented limited predictive performance. Only 1 model met the acceptability criteria (median PE ≤ ±20% and median absolute PE ≤30%). There was no difference between the data used for building the models (therapeutic drug monitoring or PK study) or the number of compartments in the models. A tendency for higher inaccuracy at low concentrations during treatment initiation was observed. Heterogeneities were observed in the predictive performances between the subpopulations, especially in terms of smoking status and sex. For the models included, BF significantly improved their predictive performance. CONCLUSIONS: Our study showed that upon external evaluation, clozapine models provide limited predictive performance, especially in subpopulations such as nonsmokers. From the perspective of model-informed prediction dosing, model predictability should be improved using updating or metamodeling methods. Moreover, BF substantially improved model predictability and could be used for clozapine treatment optimization.

Precision-medicine findings from the FACE-SZ cohort to develop motivation-enhancing programs in real-world schizophrenia.

BACKGROUND: In people with schizophrenia, major areas of everyday life are impaired, including independent living, productive activities, social relationships and overall quality of life. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. AIM: The goal of the present study was to identify factors associated with motivation deficits in real-life schizophrenia, and to assess its contribution to impaired functioning and quality of life. METHODS: Based on previous literature and clinical experience, several factors were selected and grouped into factors potentially explaining motivation deficits. Some of these variables were never investigated before in relationship with motivation deficits. RESULTS: In 561 patients with schizophrenia of the national FACE-SZ cohort living in the community, 235 (41.9%) reported severe motivation deficits. These deficits were found to be significantly associated with impaired socially useful activities, psychological and physical quality of life (in almost all domains), alcohol use disorder (aOR = 2.141, p = 0.021), severe nicotine dependence (aOR = 2.906, p < 0.001) independently of age and sex. No significant association was found for body mass index, metabolic syndrome or physical activity level. In the second model, we identified the following modifiable factors associated with motivation deficits: history of suicide attempt (aOR = 2.297, p = 0.001), positive symptoms (aOR = 1.052, p = 0.006), current major depressive episode (aOR = 2.627, p < 0.001), sleep disorders (aOR = 1.474, p = 0.024) and lower medication adherence (aOR = 0.836, p = 0.001) independently of gender, current alcohol use disorder, second-generation antipsychotics and akathisia. No significant association was found for negative symptoms, childhood trauma and inflammation. These results were maintained after removing patients with schizoaffective disorders or those with major depressive disorder. INTERPRETATION: Motivation deficits are frequent and remain persistent unmet need in real-world schizophrenia that should be addressed in future guidelines. Based on our results, literature and clinical experience, we recommend to address in priority major depression, sleep, suicide, positive symptoms (when present and as early as possible) and medication adherence to improve motivation deficits of schizophrenia.

Recommendations of the treatment-resistant depression expert center network for promoting tobacco smoking cessation based on the results from the real-world FACE-TRD national cohort.

BACKGROUND: Tobacco smoking has been associated with suicide, impulsivity and depression in non-clinical populations with differences across sexes. OBJECTIVE: To determine the role of tobacco smoking in Treatment-Resistant Depression (TRD) according to sex in a precision-medicine approach. METHOD: The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at 6 months. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at 6 months on their smoking and psychiatric hospitalization outcomes. RESULTS: 355 TRD participants were included (222 women). The smoking rate was much higher in TRD women compared to the French general population (34% vs 24%) while it was comparable for men (approximately 29%). In multivariate analyses, compared to non-smoking women, female smokers had significantly increased number of lifetime psychiatric hospitalizations (standardized beta B = 0.232, p = 0.014) and electro-convulsive therapy (adjusted odds ratio (aOR) = 2.748, p = 0.005), increased suicidal ideations (aOR = 4.047, p = 0.031), history of suicide attempt (aOR = 1.994, p = 0.033), and increased impulsivity (B = 0.210, p = 0.006) and were more frequently treated by benzodiazepines (aOR = 1.848, p = 0.035) and third- or fourth-line TRD treatments (antipsychotics aOR = 2.270, p = 0.006, mood stabilizers aOR = 2.067 p = 0.044). Tobacco smoking at baseline was predictive of psychiatric hospitalization within 6 months in persistent smoking women (aOR = 2.636, p = 0.031). These results were not replicated in men, for whom tobacco smoking was only associated with increased clinician-rated and self-reported depressive symptoms (respectively B = 0.207, p = 0.022 and B = 0.184, p = 0.048). The smoking cessation rate at 6 months was higher in women than in men (12% vs. 7%). No patient was administered nicotine substitute or varenicline at the two timepoints. INTERPRETATION: Combining these results and those of the literature, we recommend that active tobacco cessation should be promoted in TRD to improve depression, suicide and impulsivity especially in women. Female smokers appear as a specific population with heavier mental health outcomes that should be specifically addressed.

Comorbid Major Depressive Disorder in Schizophrenia: A Systematic Review and Meta-Analysis.

Comorbid major depressive disorder (MDD) in schizophrenia (SZ; SZ-MDD) has been identified as a major prognostic factor. However, the prevalence and associated factors of SZ-MDD have never been explored in a meta-analysis. All studies assessing the prevalence of SZ-MDD in stabilized outpatients with a standardized scale or with structured interviews were included. The Medline, Web of Science, PsycINFO, and Google Scholar databases were searched. Using random effects models, we calculated the pooled estimate of the prevalence of SZ-MDD. We used meta-regression and subgroup analyses to evaluate the potential moderators of the prevalence estimates, and we used the leave-one-out method for sensitivity analyses. Of the 5633 potentially eligible studies identified, 18 studies (n = 6140 SZ stabilized outpatients) were retrieved in the systematic review and included in the meta-analysis. The pooled estimate of the prevalence of SZ-MDD was 32.6% (95% CI: 27.9-37.6); there was high heterogeneity (I2 = 92.6%), and Egger's test did not reveal publication bias (P = .122). The following factors were found to be sources of heterogeneity: publication in or after 2015, the inclusion of patients from larger studies, the assessment tools, the inclusion of patients with substance use disorder or somatic chronic diseases, age, education level, the lifetime number of hospitalizations, and antidepressant use. Two-thirds of the extracted variables could not be explored due to an insufficient amount of published data. The prevalence of MDD is high among SZ individuals. Healthcare providers and public health officials should have an increased awareness of the burden of SZ-MDD.

Brain SPECT perfusion and PET metabolism as discordant biomarkers in major depressive disorder.

BACKGROUND: Brain SPECT perfusion and PET metabolism have been, most often interchangeably, proposed to study the underlying pathological process in major depressive disorder (MDD). The objective of this study was to specify similarities and inconsistencies between these two biomarkers according to global characteristics of the disease. We conducted a retrospective study in 16 patients suffering from treatment-resistant MDD who underwent, during the same current episode, a cerebral perfusion SPECT with 99mTc-HMPAO and a metabolic PET with 18F-FDG. Whole-brain voxel-based SPM(T) maps were generated in correlation with the number of depressive episodes and in correlation with the depression duration, separately for the two exams (p-voxel < 0.001 uncorrected, k > 20). RESULTS: No significant correlations were found between brain metabolism and either the number of depressive episodes or the duration of the disease, even at an uncorrected p-voxel < 0.005. On the other hand, the increased number of depressive episodes was correlated with decreased perfusion of the right middle frontal cortex, the right anterior cingulum cortex, the right insula, the right medial temporal cortex and the left precuneus. The increased depression duration was correlated with decreased perfusion of the right anterior cingulum cortex. CONCLUSIONS: This preliminary study demonstrates more significant results with brain perfusion compared with glucose metabolism in treatment-resistant MDD, highlighting the value of brain SPECT despite less favourable instrumentation detection compared to PET.

Microbiota-Orientated Treatments for Major Depression and Schizophrenia.

BACKGROUND AND SIGNIFICANCE: There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy is thus needed to improve the SZ prognosis. Microbiota-orientated treatments are currently one of the most promising tracks. METHOD: This work is a systematic review synthetizing data of arguments to develop microbiota-orientated treatments (including fecal microbiota transplantation (FMT)) in major depression and schizophrenia. RESULTS: The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments. Probiotics have yielded medium-to-large significant effects on depressive symptoms, but it is still unclear if the effect is maintained following probiotic discontinuation. Several factors may limit MD improvement when using probiotics, including the small number of bacterial strains administered in probiotic complementary agents, as well as the presence of a disturbed gut microbiota that probably limits the probiotics' impact. FMT is a safe technique enabling to improve microbiota in several gut disorders. The benefit/risk ratio of FMT has been discussed and has been recently improved by capsule administration. CONCLUSION: Cleaning up the gut microbiota by transplanting a totally new human gut microbiota in one shot, which is referred to as FMT, is likely to strongly improve the efficacy of microbiota-orientated treatments in MD and schizophrenia and maintain the effect over time. This hypothesis should be tested in future clinical trials.

The Role of Inflammation in the Treatment of Schizophrenia.

Background: Inflammation plays a major role in the onset and maintenance of schizophrenia. The objective of the present work was to synthetize in a narrative review the recent findings in the field of inflammation in schizophrenia and their application in daily practice. Method: This review was based on the most recent meta-analyses and randomized controlled trials. Results: The disturbed cytokines depend on the phase of the illness. A meta-analysis of cytokines in schizophrenia found higher levels of pro-inflammatory and anti-inflammatory cytokines in the peripheral blood in both patients with first-episode schizophrenia and relapsed patients than in healthy controls. Exploring detailed data on immune-inflammatory disturbances in SZ reveals that IL-6 is one of the most consistently disturbed cytokines. Other cytokines, including IL1, TNF, and IFN, are also disturbed in schizophrenia. Choosing a broad spectrum anti-inflammatory agent that may inhibit subsequent pathways might be particularly useful for the treatment of inflammatory schizophrenia. Highly sensitive C-Reactive Protein is a useful screening marker for detecting inflammation in SZ subjects. Anti-inflammatory agents have shown effectiveness in recently published meta-analyses. Only one study found a significant difference between celecoxib and placebo, but two found a trend toward significance on illness severity and one on positive symptoms. In addition, other published and unpublished data were included in another meta-analysis that concluded the significant effect of add-on celecoxib in positive symptoms in first episode patients. There is a lack of data to determine if aspirin is truly effective in schizophrenia to date. Other anti-inflammatory agents have been explored, including hormonal therapies, antioxidants, omega 3 fatty acids, and minocycline, showing significant effects for reducing total, positive, and negative score symptoms and general functioning. However, each of these agents has multiple properties beyond inflammation and it remains unclear how these drugs improve schizophrenia. Conclusion: The next step is to tailor anti-inflammatory therapy in schizophrenia, with two main challenges: 1. To provide a more efficient anti-inflammatory therapeutic approach that targets specific pathways associated with the pathology of schizophrenia. 2. To develop a more personalized approach in targeting patients who have the best chance of successful treatment.

Sexual dysfunctions in schizophrenia: Beyond antipsychotics. A systematic review.

BACKGROUND: Sexual dysfunctions (SD) in schizophrenia are frequent with strong impact on adherence and quality of life. Current recommendations stipulate to switch to prolactin-sparing antipsychotic in case of SD. OBJECTIVES: To synthetize in a systematic review data on the SD prevalence and the associated risk factors in schizophrenia (SZ). METHODS: Medline, Google Scholar, PsychInfo, and Cochrane were explored, without any year or language restriction. RESULTS: Overall, 89 studies and 25,490 participants were included in the present review. SZ subjects aged 18-70 reported high SD frequency [30%-82%] (men [33%- 85%]; women [25%- 85%]). For SZ men erectile dysfunction [31%-95%] was the most frequent SD vs. loss of libido for women [31%-100%]. The following risk factors were associated with increased SD: 1. Illness severity (including psychotic symptomatology, early age at SZ onset, negative symptomatology, and continuous illness course), 2. Depressive symptomatology 3. Antipsychotics (especially first generation antipsychotics, risperidone and antipsychotic polytherapy). Switching to prolactin-sparing antipsychotics has shown effectiveness in some studies (especially aripiprazole). Antidepressants were not found to be associated with SD in SZ subjects. CONCLUSION: The prevalence of SD is high in SZ subjects. In addition to the current guidelines, the present review suggests that treating depressive symptoms may be a major intervention to improve SD in SZ subjects. Sociodemographic variables, physical illnesses, metabolic syndrome and peripheral inflammation have been poorly or never explored and should be included in future studies.

Neuroleptic malignant syndrome following reintroduction of an antipsychotic after overdose.

Neuroleptic malignant syndrome (NMS) is a potentially lethal adverse drug reaction. We report a case of NMS potentially induced by dehydration in a female patient suffering from schizoaffective disorder. We discuss possible aetiologies and triggering factors alongside the existing literature.