Difference of Symptoms Networks in Early and Late Phase Schizophrenia; A Cross-Sectional Network Analysis.

OBJECTIVE: The functional remission or recovery of schizophrenia patients is a challenging task which relies on pharmacotherapy but also on the timing of psychotherapy and other therapeutic interventions. The study aimed to assess the difference in strength and structure of symptoms networks between early and late phase schizophrenia. Our secondary objective was to check whether the overall, positive, negative, and general symptoms severity change over the course of treatment and disorder. METHODS: This nested cross-sectional analysis combined the samples from two studies performed during 2014-2016 at University Psychiatric Hospital Vrapce, Zagreb, Croatia on the consecutive sample of men 30-60 years old diagnosed with schizophrenia, 85 of them in the early (≤5 years from diagnosis), and 143 in the late phase of the illness. The study was funded by the project: "Biomarkers in schizophrenia - integration of complementary methods in longitudinal follow up of FEP patients". RESULTS: Median (IQR) age of the participant in the early phase was 36 (32-45) years and in the late phase 44 (38-49) years. Patients in the early phase had significantly higher odds for being in the symptomatic remission compared to the patients in the late-phase schizophrenia (OR=2.11; 95% CI 1.09-4.09) and had 10% less pronounced negative symptoms. The global strength, density, and structure of the symptoms network were not significantly different between the two study groups. CONCLUSIONS: Negative symptoms severity change with the course of illness and differ from the early to the late phase of schizophrenia. However, the overall network of psychotic symptoms is relatively stable, and overall strengths or density and the partial relationship between particular symptoms do not change significantly. The observed worsening of negative symptoms is probably at least partially caused by the lack of clear guidelines and effective treatment options aimed specifically toward negative symptoms.

Neurocognitive Profiles of Patients with the First Episode of Psychosis and Schizophrenia Do not Differ Qualitatively: a Nested Cross-Sectional Study.

BACKGROUND: The aim of study was to analyze neurocognitive profiles in patients with first-episode psychosis (FEP) and patients with schizophrenia (SCH), and their correlations with other clinical features. SUBJECTS AND METHODS: We performed a multicentric cross sectional study including 100 FEP and 100 SCH recruited from three Croatian hospitals during 2015-2017. Assessment included a set of neurocognitive tests, psychiatric scales and self-reporting questionnaires. The main analysis was done by multigroup latent profile analysis. RESULTS: Multigroup latent profile analysis resulted in three structurally equivalent neurocognitive profiles ("Best", "Medium", "Worst"), with differences in the severity of neurocognitive deficits measured with successfulness in solving domain specific tasks. The "Best" profile was statistically significantly more prevalent in FEP and "Worst" profile in the SCH. Negative symptom score was the highest in patients with the "Worst" profile and the lowest among those with the "Best" profiles. CONCLUSIONS: Differences in neurocognitive profiles between FEP and SCH appear to be quantitative rather than qualitative nature, possibly reflecting a specific trait of illness that may progress over time. Defining neurocognitive profiles from the first episode of psychosis could help in tailoring individualized treatment options with focus on neurocognitive and negative symptoms and possible influence on patients' overall clinical outcome.

An Unusual Case of Infertility: Urethral Coitus Due to Cribriform Hymen.

Urethral coitus is a rare type of sexual practice, usually due to vaginal agenesis or hymeneal anomalies. We report a case of urethral coitus in a healthy couple who were evaluated for infertility. The female partner had cribriform hymen and dilated urethral orifice but did not report any problems except infertility and her genital anatomy was normal. The male partner reported concerns over his penile size but was otherwise healthy. After incision of hymen, they were able to have vaginal coitus and successfully conceived. While urethral coitus is rare, it should be suspected in women presenting with infertility and a dilated urethral orifice.

Treatment patterns of schizophrenia based on the data from seven Central and Eastern European Countries.

OBJECTIVE: The aim is to analyze how schizophrenia is pharmacologically treated in seven CEE countries: Croatia, Estonia, Hungary, Poland, Serbia, Slovakia and Slovenia. METHODS: Psychiatrists from selected centers in each of participating countries were asked to complete a pre-defined questionnaire on their current clinical practice. Information on protocols and resource utilization in schizophrenia treatment was included and derived from randomly selected patient medical records. Expert opinions on country-wide treatment patterns were additionally sought. This sub-analysis focuses on pharmacological treatment patterns in the last six months and over the course of the disease. RESULTS: 961 patients' data show that during last six months the most commonly prescribed medications were oral atypical antipsychotics: olanzapine (n=268), clozapine (n=234) and risperidone (n=160). The most frequently prescribed atypical antipsychotics over course of disease were: risperidone (54.5%), olanzapine (52.4%) and clozapine (35.1%), along with haloperidol (39.3%). Experts reported risperidone (four countries) and olanzapine (three countries) as first-line treatment, with the same two medications prescribed as second-line treatment. Clozapine was the most reported medication for refractory patients. Approximately 22% of patients received polypharmacy with antipsychotics in at least one period over the disease course. Mean time since diagnosis was 13.1 years and on average 4.8 treatment courses received during that period. Anxiolytics (70%), antidepressants (42%), mood-stabilizers (27%) were also prescribed, with diazepam (35.4%), sertraline (10.5%), valproic acid (17.5%) the most commonly reported, respectively, in each group. The most frequently reported treatment change was switch from one oral atypical antipsychotic to another (51%). CONCLUSION: Oral atypical antipsychotics, mostly older drugs (risperidone, olanzapine, clozapine), were most commonly prescribed for schizophrenia treatment in participating countries. Given that results are from the first large-scale analysis of RWD, we believe these findings can be a benchmark for future real-world studies, which could contribute to the optimization of treatment for this debilitating disease.

Schizophrenia causes significant burden to patients' and caregivers' lives.

BACKGROUND: Schizophrenia is a serious public health problem and is ranked among the most disabling diseases in the world. The sub-study presented here was part of a larger project to characterize the burden of schizophrenia on healthcare systems and on individuals living with the disease in Central and Eastern Europe (CEE). AIMS: This sub-study aimed to assess and analyze the impact of schizophrenia on many aspects of the lives of patients and caregivers. METHODS: Psychiatrists from selected centers in seven Central and Eastern European countries were asked to complete a questionnaire in order to collect information about the disease history, characteristics, treatment protocols and resources used for each randomly selected patient. All data were statistically analyzed and compared between countries. RESULTS: Data from 961 patients with schizophrenia (mean age 40.7 years, 45.1% female) were included in the analysis. The mean number of days spent in hospital per patient per year across all seven countries was 25.3 days. Hospitalization occurred on average once per year, with psychiatrist visits 9.4 times per year. Of the patients in the study, 61% were single, 12% divorced and 22% married or cohabiting. Almost 84% were living with relatives or a partner; only 17% lived alone and, on average, 25% of patients received support from social workers. Relatives provided care for approximately 60% of patients and 4% of them had to stop working in order to do so. Twenty-nine percent of the patients were unemployed, and 56% received a disability pension or were retired, with only 19% in full-time employment or education. CONCLUSION: Schizophrenia has a significant effect on the lives of patients and caregivers and impacts their social integration.

INSIGHT AND SELF-STIGMA IN PATIENTS WITH SCHIZOPHRENIA.

Poor insight and high level of self-stigma are often present among patients with schizophrenia and are related to poorer treatment adherence, poorer social function and rehabilitation, aggressive behavior, higher level of depression, social anxiety, lower quality of life and self-esteem. Reports on a relationship between insight and stigma are controversial. We examined the relationship of the level of insight and self-stigma in a sample of 149 patients with schizophrenia. Insight was measured with the Scale to assess Unawareness of Mental Disorder and self-stigma with the Internalized Stigma of Mental Illness. Results showed 88.6% of the patients to have high or moderate insight, with a mean value of 2.73. General insight showed the highest level (2.58) and insight in positive symptoms the lowest level (2.9). The self-stigma score in general was 2.13, with stereotype endorsement being lowest (1.98). According to study results, 77.1% of patients felt minimal or low self-stigma across all subscales, except for stigma resistance subscale. Statistically significant correlation was found between insight and four subscales of self-stigma, while no correlation was found for the stigma resistance subscale only. These results imply the need of individually tailored antistigma and insight promoting programs for patients with schizophrenia.

Testosterone levels and clinical features of schizophrenia with emphasis on negative symptoms and aggression.

BACKGROUND: Aggressive behavior and negative symptoms are two features of schizophrenia that may have a hormonal basis. AIM: The aim of this study was to compare testosterone level with clinical features of schizophrenia, focusing on negative symptoms and aggressive behavior. METHODS: The study population consisted of 120 male schizophrenic patients (ages 18-40) classified into non-aggressive (n = 60) and aggressive (n = 60) groups. Depending on the type of aggression that was manifested prior to admission, the aggressive group was divided into violent (n = 32) and suicidal (n = 28) subgroups. Psychopathological severity, violence and suicidality were assessed using the Positive and Negative Syndrome Scale (PANSS), Overt Aggression Scale and Columbia Suicide Severity Rating Scale, respectively. Total serum testosterone level was determined on the same morning that symptoms were assessed. RESULTS: In the non-aggressive group, testosterone level was negatively correlated with the score on the negative subscale of PANSS (P = 0.04) and depression (P = 0.013), and positively correlated with excitement (P = 0.027), hostility (P = 0.02) and impulsive behavior (P = 0.008). In the aggressive group, testosterone level had non-significant correlation with these parameters, and with violent or suicidal behavior. CONCLUSIONS: The results confirmed that non-aggressive male schizophrenic patients with lower levels of testosterone had a greater severity of negative symptoms. In aggressive patients, there was no correlation between testosterone and clinical features of the disorder or the degree or type of aggression. These findings indicate that therapeutic strategies targeting testosterone could be useful in the treatment of negative symptoms of schizophrenia.

Association between total serum cholesterol and depression, aggression, and suicidal ideations in war veterans with posttraumatic stress disorder: a cross-sectional study.

AIM: To investigate the relationship between total serum cholesterol and levels of depression, aggression, and suicidal ideations in war veterans with posttraumatic stress disorder (PTSD) without psychiatric comorbidity. METHODS: A total of 203 male PTSD outpatients were assessed for the presence of depression, aggression, and suicidality using the 17-item Hamilton Depression Rating Scale (HAM-D17), Corrigan Agitated Behavior Scale (CABS), and Scale for Suicide Ideation (SSI), respectively, followed by plasma lipid parameters determination (total cholesterol, high density lipoprotein [HDL]-cholesterol, low density lipoprotein [LDL]-cholesterol, and triglycerides). PTSD severity was assessed using the Clinician-Administered PTSD Scale for DSM-IV, Current and Lifetime Diagnostic Version (CAPS-DX) and the Clinical Global Impressions of Severity Scale (CGI-S), before which Mini-International Neuropsychiatric Interview (MINI) was administered to exclude psychiatric comorbidity and premorbidity. RESULTS: After adjustments for PTSD severity, age, body mass index, marital status, educational level, employment status, use of particular antidepressants, and other lipid parameters (LDL- and HDL- cholesterol and triglycerides), higher total cholesterol was significantly associated with lower odds for having higher suicidal ideation (SSI≥20) (odds ratio [OR] 0.09; 95% confidence interval [CI] 0.03-0.23], clinically significant aggression (CABS≥22) (OR 0.28; 95% CI 0.14-0.59), and at least moderate depressive symptoms (HAM-D17≥17) (OR 0.20; 95% CI 0.08-0.48). Association of total cholesterol and HAM-D17 scores was significantly moderated by the severity of PTSD symptoms (P<0.001). CONCLUSION: Our results indicate that higher total serum cholesterol is associated with lower scores on HAM-D17, CABS, and SSI in patients with chronic PTSD.

Prevalence of anxiety and depression in caregivers of Alzeheimer's dementia patients.

Alzheimer's dementia (AD) is the most common neurodegenerative disorder, which affects 30 million people worldwide. With aging of the population, it is becoming an increasing problem in Croatia. Alzheimer's dementia represents not only problem for the patient but affects the patients' caregivers as well. Caring for a patient with AD carries a significant physical, socioeconomic and psychological burden. Previous studies have shown an increased risk of physical and psychiatric illness. The aim of our study was to evaluate the prevalence and intensity of anxious and depressive symptoms in caregivers of AD patients treated at Vrapce University Psychiatric Hospital in Zagreb. The study included 30 caregivers of AD patients. Participants were included consecutively, during July and August 2010. The Croatian version of the Hospital Anxiety and Depression Scale (HADS) was used to assess the level of anxiety and depression in study participants. The mean level of anxiety and depression as measured by HADS was 10.46 +/- 4.26 and 8.03 +/- 4.08, respectively. A pathologic level of anxiety was found in 14 (46.7%) and pathologic level of depression as measured by HADS in 8 (26.7%) caregivers. This study showed that not only appropriate treatment of AD patients is necessary, but AD patient caregivers should also be provided due care and support.

Treatment-resistant schizophrenia and DAT and SERT polymorphisms.

One fifth to one third of all patients diagnosed with schizophrenia are resistant to drug treatment, which makes it a major clinical challenge. Genetic studies have focused on the association between treatment resistant schizophrenia (TRS) and a number of candidate genes, including serotonin and dopamine system genes. We explored associations between carefully characterized TRS and DAT-VNTR, SERT-PR and SERT-in2 polymorphisms. There were 173 patients enrolled in the study that were clinically evaluated using Positive and Negative Syndrome Scale and Clinical Global Impressions Scales and divided into two groups based on treatment resistance (92 patients in TRS group). Patients with a combination of SERT-in2 ll and DAT 9/10, 9/11, 9/9 and 6/6 genotypes were more likely to have TRS, compared to those with 10/10 or 10/12 genotype (OR=5.1; 95% CI=1.6-16.8). In the group of patients with DAT 10/10 or 10/12 genotype, those who also shared SERT-in2 ls or ss genotype were more likely to have TRS, compared to ll genotype carriers (OR=2.7; 95% CI=1.0-7.0). The model in which interaction between SERT-in2 and DAT polymorphisms is linked to TRS can possibly explain contradictory previous results regarding role of DAT and SERT in TRS, but further research is needed.

Alcohol abuse as the strongest risk factor for violent offending in patients with paranoid schizophrenia.

AIM: To determine predictive risk factors for violent offending in patients with paranoid schizophrenia in Croatia. METHOD: The cross-sectional study including male in-patients with paranoid schizophrenia with (N=104) and without (N=102) history of physical violence and violent offending was conducted simultaneously in several hospitals in Croatia during one-year period (2010-2011). Data on their sociodemographic characteristics, duration of untreated illness phase (DUP), alcohol abuse, suicidal behavior, personality features, and insight into illness were collected and compared between groups. Binary logistic regression model was used to determine the predictors of violent offending. RESULTS: Predictors of violent offending were older age, DUP before first contact with psychiatric services, and alcohol abuse. Regression model showed that the strongest positive predictive factor was harmful alcohol use, as determined by AUDIT test (odds ratio 37.01; 95% confidence interval 5.20-263.24). Psychopathy, emotional stability, and conscientiousness were significant positive predictive factors, while extroversion, pleasantness, and intellect were significant negative predictive factors for violent offending. CONCLUSION: This study found an association between alcohol abuse and the risk for violent offending in paranoid schizophrenia. We hope that this finding will help improve public and mental health prevention strategies in this vulnerable patient group.

Self-reported emotional and behavioral symptoms, parent-adolescent bonding and family functioning in clinically referred adolescent offspring of Croatian PTSD war veterans.

The presence of posttraumatic stress disorder (PTSD) in male war veterans has been linked with family dysfunction and psychopathology in their children [1, 2]. This study aimed to evaluate self-reported emotional and behavioral symptoms, parent-adolescent bonding and family functioning in clinically referred adolescent offspring of Croatian PTSD war veterans and determine the degree that parent-child bonding and family functioning contributed to adolescent behavior problems. Internalizing and externalizing behavior problems, parent-child bonding and family functioning were assessed in a sample of clinically referred Croatian PTSD veterans adolescent offspring (N = 122) and non-PTSD veteran adolescent offspring (N = 122) matched for age, sex, educational level, family income, parental employment status, ethnicity, and residential area. Youth Self-Report, Parental Bonding Instrument, Family Assessment Device were used. Adolescent offspring of PTSD veterans reported having significantly more internalizing and externalizing problems than non-PTSD veteran offspring, and also more difficulties in their family functioning, lower levels of maternal and paternal care, and more impaired mother-child and father-child bonding than control subjects. Internalizing symptoms were associated with family dysfunction, while externalizing symptoms were associated with paternal overcontrol/overprotection, and low maternal and paternal care. In conclusion, the increase in internalizing and externalizing symptoms as well as family and parental dysfunction among clinically referred adolescent offspring of PTSD veterans compared to their non-PTSD veteran counterparts indicates a need for early detection and interventions targeting both adolescent psychopathology and family relationships.

The relationship between depressive syndrome and suicidal risk in patients with acute schizophrenia.

AIM: To determine the relationship between scores on five factors of the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression scale for Schizophrenia (CDSS) and scores on the InterSePT Scale for Suicidal Thinking (ISST) in patients with acute schizophrenia. METHODS: Data were collected on sociodemographic and clinical characteristics of 180 drug-treated in-patients with acute schizophrenia. Their symptoms were assessed with PANSS, CDSS, and ISST and correlations between the scores were calculated. Statistically significant correlations were included in the logistic regression analysis to identify predictors of suicidal risk. RESULTS: CDSS (P<0.001) score and negative (P<0.001), disorganized (P=0.041), emotional (P<0.001), and total score on PANSS (P<0.001) showed a significant positive correlation with ISST. Stepwise logistic regression analysis revealed that CDSS scores (odds ratio [OR] 5.18; confidence interval [CI] 1.58-16.95), and disorganized (0.90; 0.81-0.99) and emotional (1.15; 1.01-1.30) factors of PANSS were predictors of suicidal risk. CONCLUSION: Our results suggested a considerable association between depressive syndrome as assessed by the PANSS emotional factor and CDSS score and suicidal risk in patients with acute schizophrenia.

Importance of the newer generations of antipsychotics in reducing schizophrenia hospitalization rates.

Throughout history, given the lack of understanding of schizophrenia and lack of effective treatment options, patients were often committed to asylums and later psychiatric institutions, often for prolonged periods of time. First antipsychotic medications helped to bring about changes in approach to these patients and facilitated deinstitutionalization, and discovery of new drugs with differing side-effects profiles introduced new options in treating schizophrenia patients. Data on hospitalization of patients in University Psychiatric Hospital Vrapce from the mid-1990s, as well as data on national level, suggests a trend of drop in hospitalization of schizophrenia patients. At the same time, that period saw significant increase in a number of available newer-generations antipsychotics and the rise in their use compared to first-generation one. Although far from being the only contributing factor, seem to play an important role in continuing the trend of reducing hospitalization rates for schizophrenia patients that started with first antipsychotics. Newer antipsychotics with a more tolerable side-effects profile promote better compliance and further reduce rate of relapse and hospitalizations. No less important is the contribution of newer antipsychotics with new receptor profiles to the personalized psychopharmacotherapy approach that is in tune with emerging conceptualizations of schizophrenia as a complex syndrome with a number of separate symptom domains, whose specific combinations produce specific individual clinical presentation and in turn ask for a specific individual approach to the patient.

Cobalamin deficiency manifested with seizures, mood oscillations, psychotic features and reversible dementia in the absence of typical neurologic and hematologic signs and symptoms: a case report.

Cobalamin deficiency is associated with a wide spectrum of hematologic, neurologic, gastroenterologic and psychiatric disorders or symptoms. We report a case of a 50-year-old man with complex partial seizures with secondary generalization, mood oscillations and psychotic symptoms alternating with confusion and reversible dementia secondary to cobalamin deficiency in the absence of typical neurologic and/or hematologic symptoms and signs. Exclusion of epilepsy, acute, atrophic or expansive lesion of central nervous system and usual etiology associated with reversible dementia (infectious diseases, an endocrine etiology and deficiency of vitamins other than cobalamin); finding of cobalamin deficiency only and complete neuropsychiatric recovery after substitution, confirmed etiology. Typical and atypical psychiatric manifestations due to cobalamin deficiency that precede neurologic and/or hematologic signs and symptoms can recover completely after adequate replacement therapy.

Cost-Utility Analysis of Depot Atypical Antipsychotics for Chronic Schizophrenia in Croatia.

OBJECTIVES: As a nation with a developing economy, Croatia is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. We conducted a pharmacoeconomic analysis to determine the cost-effectiveness of atypical depots in Croatia. METHODS: A 1-year decision-analytic framework modeled drug use. We determined the average direct cost to the Croatian Institute for Health Insurance of using depot formulations of paliperidone palmitate long-acting injectable (PP-LAI), risperidone LAI (RIS-LAI), or olanzapine LAI (OLZ-LAI). An expert panel plus literature-derived clinical rates populated the core model, along with costs adjusted to 2012 by using the Croatian consumer price index. Clinical outcomes included quality-adjusted life-years, hospitalization rates, emergency room treatment rates, and relapse days. Robustness of results was examined with one-way sensitivity analyses on important inputs; overall, all inputs were varied over 10,000 simulations in a Monte Carlo analysis. RESULTS: Costs (quality-adjusted life-years) per patient were €5061 (0.817) for PP-LAI, €5168 (0.807) for RIS-LAI, and €6410 (0.812) for OLZ-LAI. PP-LAI had the fewest relapse days, emergency room visits, and hospitalizations. Results were sensitive against RIS-LAI with respect to drug costs and adherence rates, but were generally robust overall, dominating OLZ-LAI in 77.3% and RIS-LAI in 56.8% of the simulations. CONCLUSIONS: PP-LAI dominated the other drugs because it had the lowest cost and best clinical outcomes. Compared with depots of olanzapine and risperidone and oral olanzapine, PP-LAI was the cost-effective atypical LAI for treating chronic schizophrenia in Croatia. Using depot paliperidone in place of either olanzapine or risperidone would reduce the overall costs of caring for these patients.

Impact of destruction of classic moral principles on ethical questions in psychiatry.

Society's treatment of psychiatric patients was always a reflection of social development and social awareness, as well as of ethical principles dominating a certain time period in that society. Over the last two and a half millennia, during which principles of Hippocratic ethics applied, attitudes towards psychiatric patients, from an ethical and practical standpoint, were and still are controversial to say the least. During this period thousands of people with mental disorders were abused, tortured, or killed, all of this in accordance to the existing ethical and legislative norms (Malleus Maleficarum, eugenic laws of totalitarian regimes...). In the last forty years many international organizations and associations brought forth a number of resolutions and declarations warning of the position and of the rights of psychiatric patients and giving instructions on the humane, that is to say ethical, treatment of this category of patients. In almost all the western countries laws are passed to protect the rights of people with mental disorders. Thanks to this and maybe even more to the development of psychiatry as a medical and scientific profession, the position of those with mental disorders is improving. However, at the same time over the last 40 years we are witnesses to the destruction of the classic moral principles and the establishment of certain "new" ethics which put psychiatric patients at a disadvantage, only in a more subtle way then before. This is why it is important to reexamine many of the ethical questions in psychiatry in the context of present ethical controversy.

Familial risk factors favoring drug addiction onset.

This study, primarily aimed at identification of familial risk factors favoring drug addiction onset, was carried out throughout 2008 and 2009. The study comprised a total of 146 addicts and 134 control subjects. Based on the study outcome, it can be concluded that in the families the addicts were born into, familial risk factors capable of influencing their psychosocial development and favoring drug addiction onset had been statistically more frequently encountered during childhood and adolescence as compared to the controls. The results also indicated the need for further research into familial interrelations and the structure of the families addicts were born into, as well as the need for the implementation of family-based approaches to both drug addiction prevention and therapy.

Flexible dosing with paliperidone ER in the treatment of patients with acutely exacerbated schizophrenia: results from a single-arm, open-label study.

OBJECTIVE: To extend findings from fixed-dose, double-blind, placebo-controlled clinical trials in selected patient populations by using flexibly-dosed oral paliperidone extended-release (ER) in a more naturalistic setting. METHODS: Adults hospitalized with an acute exacerbation of schizophrenia were prospectively treated with open-label flexibly-dosed paliperidone ER 3-12 mg/day for 6 weeks. RESULTS: Overall, 294 patients were treated. The primary endpoint, defined as ≥30% improvement in Positive and Negative Syndrome Scale total scores from baseline to endpoint, was achieved by 66.3% of patients. The percentage of patients rated as at least 'markedly ill' in Clinical Global Impression of Severity scale decreased from baseline (74.1%) to endpoint (20.0%). Patient functioning, assessed by the Personal and Social Performance scale, improved significantly from 50.0 ± 14.3 at baseline to 63.6 ± 14.9 at endpoint (p < 0.0001). Concomitant benzodiazepines were newly initiated in 191 patients (65.0%), and new concomitant medications other than benzodiazepines were started after baseline for 133 patients (45.2%), most frequently paracetamol, zolpidem, and zopiclone. No unexpected adverse events were identified. CONCLUSIONS: These data support findings in more selected patient populations treated with fixed-dose paliperidone ER. Flexibly-dosed paliperidone ER administered in a naturalistic hospital setting to a more representative patient population experiencing an acute episode of schizophrenia, was associated with clinically meaningful treatment response. Strength of conclusions is limited by the open-label design and lack of a comparator group. Furthermore, some of the improvements observed may in part be associated with increased attention provided to patients and concomitant use of psychotropic medications, such as benzodiazepines, during this study.