A randomized, double-blind, placebo- and risperidone-controlled study on valnoctamide for acute mania.

OBJECTIVES: Mood stabilizers administered for bipolar disorder during pregnancy, such as valproic acid, can increase the risk of congenital anomalies in offspring. Valnoctamide is a valproic acid derivative associated with a decreased risk for congenital abnormalities in animals. The present study evaluated the efficacy and safety of valnoctamide monotherapy, compared to placebo, in the treatment of patients in an acute manic episode. METHODS: A 3-week, double-blind, randomized, placebo- and risperidone-controlled, parallel group trial was conducted on 173 patients in an acute manic episode. Patients were randomized to receive valnoctamide 1500 mg/d (n=71), risperidone 6 mg/d (n=32), or matching placebo (n=70). The primary outcome measure was the change in Young Mania Rating Scale (YMRS) scores. RESULTS: Valnoctamide did not differ significantly from placebo on any of the study endpoints (YMRS, Positive and Negative Syndrome Scale, and the Clinical Global Impression Scale for Bipolar Disorder [CGI-BP] scales; all P>.60). Mixed models for repeated measures showed that risperidone produced significantly more improvement than placebo in the overall bipolar disorder CGI-BP severity scale (P=.036), and the CGI-BP severity scale for mania (P=.021). The Kaplan-Meier survival curve revealed higher all-cause discontinuation rates (mainly due to lack of efficacy) in the valnoctamide group compared to the other study groups (P=.026). Patients with higher valnoctamide plasma levels had a numerically higher YMRS response, but this was not statistically significant. CONCLUSIONS: Valnoctamide was well tolerated at 1500 mg/d but lacked efficacy in the treatment of symptoms in patients with acute mania. Possible differences between the biological mechanisms of action of valproic acid and valnoctamide are discussed.

The SWITCH study: rationale and design of the trial.

Many patients do not respond to the first antipsychotic drug prescribed, but require multiple trials with different drugs before response is achieved. Current treatment guidelines vary substantially in their recommendations as to how long clinicians should wait before an antipsychotic treatment attempt should be considered as failed and the compound switched. It has, however, recently been shown that poor early response to an antipsychotic is associated with continuous poor later response in the course of the same treatment attempt. This finding suggests that patients who do experience poor early response might benefit from a switch in antipsychotic medication as early as 2 weeks after treatment initiation. In the SWITCH trial, 350 patients suffering from an acute episode of schizophrenia are randomly assigned to double-blind treatment with either olanzapine or amisulpride. The primary endpoint is symptomatic remission at week 8. Patients not experiencing at least minor response after 2 weeks are randomized again to either staying on the initially assigned drug or being switched to the alternative compound for another 6 weeks. In case early switching proves superior to maintaining treatment, time wasted for unsuccessful treatment attempts could be minimized, patients' outcomes improved, duration of hospital stays reduced, and thus overall treatment expenses saved. The current report will present the methods of the trial, focusing on various specific features which could be adopted by future studies.

Is non-pharmacological treatment an option for certain schizophrenia patients?

BACKGROUND: Schizophrenia treatment has been debated at length and presently pharmacological treatment is being advocated as the most beneficial for patients. However, research has shown contradictory results regarding the suitability of pharmacological treatment for certain groups of schizophrenia patients. METHODS: The present review discusses results from the literature indicating good outcomes only for patients who adhered to prescribed pharmacological treatments. It also describes studies favoring non-drug treatments in certain schizophrenic patients. RESULTS: The authors described two groups of patients where the long-term use of neuroleptics may be useless, if not harmful. The first group comprised schizophrenic people with a single psychotic episode and therefore very good prognosis. In their case, the prolonged use of antipsychotics would not be beneficial due to pharmacological and social (stigma) side effects. Further research is warranted to identify and investigate biological, environmental, and psychological factors associated with single-episode schizophrenia. The second group comprised ultra-resistant schizophrenic patients. In their case, in the absence of a therapeutic response in acute episodes or aggressive behavior, clinicians should use short episodes of treatment with benzodiazepines or other sedative medications such as mood stabilizers. CONCLUSIONS: The present paper attempted to answer the important question as to whether all schizophrenic people should be treated with antipsychotics for the same good prognosis. The authors have provided solutions for better outcomes in a greater number of patients using alternative treatment after identifying schizophrenic patients who should not receive neuroleptic treatment. Suggestions for future research are also discussed.

Quality of Life in People With Subjective Cognitive Decline.

Objective: Quality of life is extensively studied in older persons, but there are few studies that investigate it in people with subjective cognitive decline. Our aim was to evaluate the quality of life in a Romanian sample of individuals with subjective cognitive decline compared to controls while accounting for different possible moderators. To our knowledge, this is the first study to evaluate the quality of life in a Romanian subjective cognitive decline sample. Methods: We conducted an observational study to evaluate differences in the quality of life between subjective cognitive decline and controls. Participants were evaluated for subjective cognitive decline according to Jessen et al. We collected sociodemographic and clinical characteristics and information about physical activity. Quality of life was evaluated using the Short Form-36 questionnaire. Results: There were 101 participants included in the analysis with 66.33% (n = 67) in the subjective cognitive decline group. There were no differences between the social, demographic, and clinical characteristics of the individuals. The subjective cognitive decline group had a higher score on the negative emotion trait of Big Five. Individuals with subjective cognitive decline reported poorer physical functioning (P = .034), more role limitations due to physical health (P = .010) and emotional problems (P = .019), and less energy (P = .018) compared to the control group. Conclusion: Persons with subjective cognitive decline reported diminished quality of life compared to controls and differences were not explained by other sociodemographic and clinical characteristics evaluated. This area could prove to be an important target for nonpharmacological interventions in the subjective cognitive decline group.

Risk factors for involuntary admission in a Romanian patient sample.

BACKGROUND: Involuntary admission is widely used in psychiatry, usually requiring that the patient present an imminent danger to himself or others. Previous studies have established several predictors for involuntary admission, but they have been almost exclusively conducted in Western European or North American countries. By contrast, data on this topic from Eastern European countries is virtually absent. Historically, involuntary admission has been often used as a tool for political repression in Romania before the fall of the communist regime. While there have been significant changes in the legal framework in the last 30 years, there is still no real-world data to build upon. METHODS: We analyzed a sample of 177 patients admitted to the "Alexandru Obregia" psychiatric hospital in Bucharest between November 2022 and January 2023, of which 49.7% (88) were involuntary hospitalizations. We collected socio-demographic and clinical data by both by direct interview, and by consulting patient records, attending physicians and relatives. RESULTS: Socio-demographic factors predictive for involuntary admission were unemployment, lower income, and urban living. Of the clinical variables analyzed, diagnosis of psychosis or mania on admission carried increased risk of involuntary hospitalization, as did nonadherence to treatment, higher disease severity and aggression. Hospital presentation by police or ambulance carried significant additional risk compared to self-referral. CONCLUSION: Certain categories of patients are considerably more likely to be involuntarily hospitalized and there appears to be considerable interrelatedness between the identified risk factors.

A randomized controlled trial of add-on naproxen, simvastatin and their combination for the treatment of schizophrenia or schizoaffective disorder.

This large randomized controlled trial examined the effect of naproxen, simvastatin or both on patients with schizophrenia. This was a large multi-center, twelve-week, randomized, double-blind, placebo-controlled, four-arm clinical trial administering naproxen, simvastatin or both to 232 subjects with schizophrenia or schizoaffective disorder. The primary outcome was change in PANSS total score. ANCOVA and mixed model analyses of the PANSS total score change showed no significant difference between naproxen and placebo (adjusted p = 0.78), simvastatin and placebo (adjusted p = 0.38) or the combination of naproxen and simvastatin compared to placebo (adjusted p = 0.72). No statistically significant drug-placebo differences were found in the PANSS subscales, CGI or BACS between all groups. There was a near significant improvement in negative symptoms (p = 0.06), and an analysis of the 5 factor PANSS factors analysis found a significant improvement in simvastatin above placebo in withdrawal (p = 0.03). These finding were not significant after correcting for multiple comparisons. A meta-analysis on changes in total PANSS scores in studies on statins in schizophrenia, including the present study together with six other studies showed a significant improvement for statins compared to placebo (Hedges' G of -0.245 (CI= -0.403, -0.086, p = 0.002). When one outlying study which showed particularly strong effects of statins was removed, part of the effect went away. In conclusion, in this study, naproxen and simvastatin alone or in combination were not efficacious in the treatment of symptoms in schizophrenia. However, the meta-analysis of all studies of simvastatin for schizophrenia indicates further research on this topic.

How "Subjective" is Subjective Cognitive Decline?

Background: Subjective cognitive decline is presently considered to be the earliest clinical stage of neurodegeneration. By its current definition, subjective cognitive decline conceptually implies that the sufferer presents no psychometrically measurable cognitive impairment despite numerous articles stating the presence of discrete objective impairments. Our purpose was to evaluate differences in objective cognitive performance in subjective cognitive decline patients compared to healthy controls. Methods: A total of 101 cognitively unimpaired participants were divided into a subjective cognitive decline group (n = 67) and healthy control group (n = 34). We conducted a thorough cognitive evaluation and collected social, demographic, and clinical data as well as data on personality traits, sleep quality, and physical activity. Both groups were matched for sex, age, education, and Mini-Mental State Examination score. Results: The subjective cognitive decline group had a lower verbal learning capacity as shown by the worse performance on Rey auditory verbal learning test trial 1 (P = .021) and Rey auditory verbal learning test total scores (P = .023). The subjective cognitive decline group was significantly more impaired in executive functioning compared to controls, as shown by trail making test A (P = .012) evaluation. Conclusion: Persons with subjective cognitive decline have subtle, objective cognitive impairments which may be undetected with widely used, brief cognitive evaluations, such as the Mini-Mental State Examination. Yet, these impairments are not severe enough to warrant the diagnosis of mild cognitive impairment. Current subjective cognitive decline criteria could be expanded in order to increase the diagnostic precision of subjective cognitive decline.

Risk factors and consequences of traumatic brain injury in a Swiss male population cohort.

OBJECTIVE: To investigate the risk factors for and the consequences (ie, substance use disorders (SUD), depression, personality traits) of traumatic brain injury (TBI) in young Swiss men. DESIGN: This is a three-wave cohort study. Risk factors were measured at baseline (2010-2012) and at follow-up 1 (FU1; 2012-2014), while the consequences and TBI were measured at follow-up 2 (FU2; 2016-2018). SETTING: Switzerland. PARTICIPANTS: All participants at FU2 (Mage=25.43, SD=1.25) of the Cohort Study on Substance Use Risk Factors (N=4881 young Swiss men after listwise deletion). MEASURES: The outcomes measured were TBI, SUD (ie, alcohol, nicotine, cannabis, other illicit drugs), depression and personality traits (ie, sensation seeking, anxiety-neuroticism, sociability, aggression-hostility) at FU2. The predictors were previous TBI (lifetime TBI but not in the past 12 months at FU2), SUD, personality traits and sociodemographics (highest level of achieved education, age, linguistic region) measured at FU1. RESULTS: At FU2, 3919 (80.3%) participants reported to never have had TBI, 102 (2.1%) have had TBI in the last 12 months (TBI new cases), and 860 (17.6%) have had TBI during their lifetime but not in the 12 months preceding FU2 (previous TBI). Low educational attainment (OR=3.93, 95% CI 2.10 to 7.36), depression (OR=2.87, 95% CI 1.35 to 6.11), nicotine dependence (OR=1.72, 95% CI 1.09 to 2.71), high sociability (OR=1.18, 95% CI 1.07 to 1.30), high aggression-hostility (OR=1.15, 95% CI 1.06 to 1.26) and high sensation seeking (OR=1.33, 95% CI 1.04 to 1.68) at FU1 were significantly associated with TBI new cases at FU2. Previous TBI was significantly associated with nicotine dependence (OR=1.46, 95% CI 1.16 to 1.83), depression (OR=2.16, 95% CI 1.56 to 2.99) and aggression-hostility (B=0.14, 95% CI >0.00 to 0.28) at FU2. CONCLUSION: Low educational attainment and depression are the most significant risk factors associated with increased odds of future TBI, while depression, nicotine dependence and high aggression-hostility are the main consequences of previous TBI. TBI should be considered an underlying factor in the treatment of depression, SUD or unfavourable personality profiles.

Add-On Pramipexole for the Treatment of Schizophrenia and Schizoaffective Disorder: A Randomized Controlled Trial.

Objective: Several small clinical trials have reported that the dopamine agonist pramipexole was beneficial in treating patients with schizophrenia. A confirmatory trial was conducted to test this hypothesis.Methods: This 16-week, multicenter, double-blind, randomized, placebo-controlled study included 200 subjects meeting DSM-IV-TR criteria for schizophrenia or schizoaffective disorder. Patients were randomized to receive either pramipexole (0.75 mg twice daily, n = 100) or placebo (n = 100) as an add-on to their regular antipsychotic treatment. The primary outcome measure was the total score on the Positive and Negative Syndrome Scale (PANSS); secondary outcome measures included PANSS subscale and cognitive functioning scores. Recruitment was performed in 30 sites in Romania and 1 site in the Republic of Moldova between January and June 2011.Results: Analysis of covariance models showed no significant difference between pramipexole and placebo for total PANSS (P > .99) and PANSS positive (P > .99), negative (P = .73), and general psychopathology (P = .99) subscale scores. Changes in Clinical Global Impressions-Severity of Illness scale and Brief Assessment of Cognition in Schizophrenia scores showed no significant difference between pramipexole and placebo.Conclusions: The results of this large randomized controlled trial indicated that pramipexole was not efficacious as an add-on to antipsychotic medications for schizophrenia.Trial Registration: ClinicalTrials.gov identifier NCT01320982.

Changing the Antipsychotic in Early Nonimprovers to Amisulpride or Olanzapine: Randomized, Double-Blind Trial in Patients With Schizophrenia.

BACKGROUND AND HYPOTHESIS: Meta-analyses have shown that the majority of patients with schizophrenia who have not improved after 2 weeks of treatment with an antipsychotic drug are unlikely to fully respond later. We hypothesized that switching to another antipsychotic with a different receptor binding profile is an effective strategy in such a situation. STUDY DESIGN: In total, 327 inpatients with an acute exacerbation of schizophrenia were randomized to double-blind treatment with either olanzapine (5-20 mg/day) or amisulpride (200-800 mg/day). Those patients who had not reached at least 25% Positive-and-Negative-Syndrome-Scale (PANSS) total score reduction from baseline after 2 weeks (the "non-improvers") were rerandomized double-blind to either staying on the same compound ("stayers") or to switching to the other antipsychotic ("switchers") for another 6 weeks. The primary outcome was the difference in the number of patients in symptomatic remission between the combined "switchers" and the "stayers" after 8 weeks of treatment, analyzed by logistic regression. STUDY RESULTS: A total of 142 nonimprovers were rerandomized at week two. 25 (45.5 %) of the 'stayers' compared to 41 (68.3 %) of the "switchers" reached remission at endpoint (p = .006). Differences in secondary efficacy outcomes were not significant, except for the PANSS negative subscore and the Clinical-Global-Impression-Scale. "Switchers" and "stayers" did not differ in safety outcomes. CONCLUSIONS: Switching "non-improvers" from amisulpride to olanzapine or vice-versa increased remission rates and was safe. The superiority in the primary outcome was, however, not paralleled by significant differences in most secondary efficacy outcomes and the effect was only apparent at the last visit making replications of longer duration necessary.

Training and retaining mental health professionals: The Romanian experience in the European Union.

BACKGROUND: Romania has been a member of the European Union since 2007. According to the World Health Organization, the national burden of mental disorders is high, with 2743.69 disability-adjusted life years per 100.000 population. Moreover, in a country of 19 million people, Romania's mental health system is currently functioning at capacity, with 5.66 adult psychiatrists/100.000 population and only 0.56 child and adolescent psychiatry (CAP) doctors per 100.000 population. METHOD: we conducted a simple narrative review of the current literature on the topic of training of psychiatry trainees in Romania. RESULTS: Undergraduate training consists of only 4 weeks of clinical and theoretical work for adult and CAP. Psychiatry postgraduate training lasts 5 years and is still duration-oriented. Psychiatric trainees mostly spend their clinical work in inpatient units due to the scarcity of other services or the lack of integration of training programs in the existing psychiatric services. Theoretical training is not nationally formalized, and, during training, yearly assessments tend to be neglected. An ongoing challenge in Romania has been retaining young career psychiatrists. CONCLUSION: Although in a trend toward improvement of health services, "brain drain" has been and continues to be a massive phenomenon among Romanian psychiatrists, mainly driven to Western-European countries due to financial reasons, various shortcomings in overall infrastructure, and because of the lack of continuous professional and personal development opportunities. As the world is currently facing an unprecedented mental health crisis, steps must be taken to improve psychiatric training, retain psychiatrists in Romania, and provide better national mental health services.

The Use of Cannabidiol in Treating Psychiatric Disorders: A Systematic Review.

Cannabidiol (CBD) has been used as a pharmacological treatment for psychiatric disorders in many studies, but few of good quality at the moment. Our objective was to assess the effect of CBD in mono/add-on therapy on symptom severity in psychiatric disorders. We performed a systematic review of clinical trials and randomized controlled trials that used CBD as treatment for psychiatric disorders. PRISMA criteria have been used for methodological purposes. Two assessors individually examined the results based on title and abstract, and decided which papers warranted full read. We included studies in English that measured disease severity as primary outcome. Out of 226 studies returned from the search, 9 warranted full read. There were 4 studies using CBD in schizophrenia, 3 studies of substance use disorder and 2 studies of social anxiety. CBD has a good safety profile even in higher doses, but results are inconclusive regarding improvements in disease severity.

Adjunctive Aspirin vs Placebo in Patients With Schizophrenia: Results of Two Randomized Controlled Trials.

Two previous randomized controlled trials (RCTs) suggested that adjunctive aspirin is efficacious in treating schizophrenia. We conducted two 16-week double-blind randomized placebo-controlled RCTs of adjunctive 1000 mg aspirin vs placebo in schizophrenia. Study 1 included 200 patients, with Positive and Negative Syndrome Scale (PANSS) total score as the primary outcome. Study 2 included 160 patients with C-reactive protein (CRP) >1 mg/L at baseline; the primary outcome was PANSS-positive score. Dropout rates for aspirin/placebo were 12% in study 1 and 20% in study 2. Differences in outcome between aspirin and placebo were calculated with linear regression, adjusting for the baseline value of the outcome. No statistically significant between-group differences were found in primary or secondary outcomes in either study. Study 1: mean difference in PANSS at 16 weeks was -3.9 (95% CI: -8.4 to 0.5, P = .10, effect size (ES) = -0.25) and at 8 weeks was -3.5 (95% CI: -7.5 to 0.5, P = .11, ES = -0.22). Study 2: mean difference in PANSS at 16 weeks was 0.3 (95% CI: -4.1 to 4.7, P = .90, ES = 0.02) and in positive PANSS was 0.5 (95% CI: -1.0 to 2.1, P = .50, ES = 0.11). A meta-analysis of these data with the existing studies, excluding one with large baseline differences in total PANSS, found that the overall estimate of the effect of adjunctive aspirin on the PANSS total score comparing group means at the end of the study was -2.9 (95% CI: -6.6 to 0.7; P = .21), favoring aspirin. Our studies and meta-analysis failed to find a statistically significant improvement in the symptoms of schizophrenia from adjunctive aspirin therapy in comparison to placebo in schizophrenia. Trial registration: study 1: Clinicaltrials.gov: NCT01320982; study 2 (high CRP): EudraCT Number: 2014-000757-36.

Clinical Validity of Subjective Clinical Prognosis in First Episode Psychosis Schizophrenia Patients: An Analysis of Data from the European First Episode Schizophrenia Trial (EUFEST) Study.

PURPOSE: This study examined the validity of subjective clinical prognosis (SCP), a commonly used clinical tool, in first episode psychosis patients included in the European First Episode Schizophrenia Trial (EUFEST) study. PATIENTS AND METHODS: The study comprised 455 patients from the EUFEST trial (mean age 25.92, SD=5.45; 188 (41.31%) women, 267 (58.69%) men). SCP was classified into three mutually exclusive groups: "good prognosis" (GP) (n=265), "average prognosis" (AP) (n=131), and "poor prognosis" (PP) (n=59). The validity of the SCP was assessed by investigating the differences between the SCP groups and completer or responder status of the patients, during 1 year of the trial. RESULTS: The proportion of completers was significantly higher in the GP group (64.4%) compared to the AP group (25.6%) (OR=1.62, 95% CI=1.062-2.476, p<0.031) and the PP group (10%) (OR=2.17, 95% CI=1.226-3.853, p<0.009) throughout the whole duration of the trial. In what concerns responsiveness, a significantly higher number of responders were registered in the GP group compared to the AP and the PP groups in the first three months of treatment, but this outcome did not persist afterwards. CONCLUSION: In terms of its predictive value at first episode schizophrenic patients, SCP seems to be reliable for treatment completion, but has a limited utility in what concerns responsiveness to treatment. This finding suggests the necessity of creating a prediction model potentially including, besides SCP, other measurement-based variables.

Knowledge of Prevention Measures and Information About Coronavirus in Romanian Male Patients with Severe Mental Illness and Severe Alcohol Use Disorder.

PURPOSE: Patients with severe mental illness (SMI) and alcohol use disorder (AUD) are at higher risk for contracting coronavirus-19 (COVID-19) and for poor outcomes of COVID-19 infection. One reason for this could be the lack of knowledge regarding preventive measures against COVID-19 and the inability of the psychiatric patients to discern misinformation from facts. PATIENTS AND METHODS: The study design was cross-sectional. We applied one questionnaire that evaluated knowledge of prevention measures and information about COVID-19 (comprised of two sections, each with five questions). The first section evaluated knowledge regarding the official WHO prevention measures against COVID-19, and the second consisted of false information about COVID-19 which examined the ability to identify misinformation about COVID-19. These questionnaires were applied face-to-face to psychiatric male inpatients from a tertiary psychiatric hospital in Bucharest diagnosed with SMI or severe alcohol disorder (SAUD) and to male controls from the community, matched by age and education. Mean scores of patients and controls were compared using Mann-Whitney test. RESULTS: There were 115 male psychiatric patients in total (65 SMI and 50 SAUD) and 57 controls included after the matching procedure. We found statistically significant lower (P<0.05) scores for psychiatric patients compared to controls regarding the prevention and general knowledge of COVID-19 (P<0.001), the WHO information about prevention measures (P=0.041), and the ability to identify misinformation about COVID-19 (P<0.001). The fact that psychiatric patients have less knowledge about prevention measures against COVID-19 and a reduced capacity to discern misinformation suggests that we need to identify new methods to convey correct information to these patients and also to better equip them to handle misinformation regarding COVID-19. CONCLUSION: Patients with SMI and SAUD are less informed regarding COVID-19 infection and preventive measures compared to controls, while being prone to believing false information about COVID-19 as well.

Raloxifene Plus Antipsychotics Versus Placebo Plus Antipsychotics in Severely Ill Decompensated Postmenopausal Women With Schizophrenia or Schizoaffective Disorder: A Randomized Controlled Trial.

OBJECTIVE: Several single-center studies have found raloxifene, an estrogen agonist, to be effective in ameliorating symptoms of schizophrenia in stable patients as augmentation of antipsychotics. This multicenter study assessed whether raloxifene plus antipsychotic treatment, in comparison to placebo plus antipsychotics, improves symptoms or cognition in severely ill decompensated schizophrenia patients. METHODS: In this 16-week, double-blind, randomized, placebo-controlled study, 200 severely ill, decompensated postmenopausal women who met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder were recruited from January 2011 to December 2012 and were randomized to receive either raloxifene 120 mg/d plus antipsychotics or placebo plus antipsychotics. The primary outcome measure was Positive and Negative Syndrome Scale (PANSS) total score at the end of the trial. RESULTS: The placebo plus antipsychotics group experienced statistically significant improvement in PANSS total score (P < .001) compared to the raloxifene plus antipsychotics group, using mixed models for repeated measures, with results favoring placebo by 4.5 points (95% CI, 2.3-6.7). These results were clearly outside the 95% confidence interval. This negative effect was more pronounced in patients who had more frequent relapses and in those with baseline PANSS scores of 100 or higher. There were no differences between groups in Clinical Global Impression Scale-Severity scores or Composite Brief Assessment of Cognition in Schizophrenia scores at 16 weeks (P > .3). Baseline follicle-stimulating hormone and estradiol levels did not alter the drug-placebo differences. CONCLUSIONS: Individuals in the active treatment arm showed worse outcome than those in the placebo arm, most likely as a result of chance variation, but the results unequivocally show no benefit of antipsychotics plus raloxifene versus antipsychotics plus placebo in this large randomized, double-blind, placebo-controlled trial in postmenopausal women. These data do not support the use of raloxifene in severely decompensated schizophrenia patients until reliable research identifies what subgroup of patients or domain of outcome is benefited. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01280305.

The Daily Functionality in a Major Depressive Episode Cohort of Romanian Patients - a Non-Interventional Study.

OBJECTIVES: The aim of this non-interventional, investigator driven study was to assess the functionality of patients with major depression under treatment with agomelatine in real life clinical practice. MATERIAL AND METHODS: The study was multicenter, non-interventional and evaluated the functionality of the adult patients with a DSM-IV diagnosis of MDD (single or recurrent episode and no treatment in the previous 6 months). It took place in Romania and it was a 10-weeks study. After the clinicians took the medical decision of treatment with agomelatine and if the patient agreed to be evaluated more accurate in this study, in order to assess functionality, patients completed at each visit the Sheehan Disability Scale (SDS). Patients were assessed also with QIDS-C (Quick Inventory of Depressive Symptomatology), a measure of depression symptoms severity and CGI scale severity (CGI-S), CGI scale improvement (CGI-I) and therapeutic index. Also, data about demographics and disease were collected during clinical interviews and from medical records. RESULTS: The functionality as assessed with SDS showed a significant functional impairment at baseline with scores >6 for each of the 3 inter-related domains of work/school, social and family life. At the end of the study, all functional aspects were improved although a mild impairment still persist requiring further treatment. A total of 1191 patients were analyzed (mean age: 47 years, 68% female). Mean QIDS-16 total score at baseline was 14.3 and decreased over the 10-week prospective period to 2.3. Most patients were treated with agomelatine. CONCLUSION: This study outcome confirms the fast on set of functionality improvement of agomelatine and further treatment need for the total remission of clinical depressive symptomatology after 10 weeks of treatment.