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Objective: The burden on caregivers of patients with severe mental disorders is significantly higher than the care burden of patients with other medical conditions. Substance use disorder is also one of the most common psychiatric disorders that has negative effects on people's quality of life. This study was designed to investigate caregiver burden in severe mental disorders versus substance use disorder. Method : First-degree relatives of patients admitted to the Razi Psychiatric Hospital of Tehran with a diagnosis of schizophrenia, bipolar disorder type1, schizoaffective disorder, or substance use disorder entered this study. They completed the sociodemographic questionnaire for patients and caregivers and the Zarit burden interview for caregivers. Results: Our study shows that caregiver burden in substance use disorder has no significant difference with that in severe mental disorders (P > 0.05). In both groups, the highest spectrum of burden was moderate to severe. To find caregiver burden related factors, a general linear regression model with multiple predictor variables was fitted. In this model, caregivers' burden was significantly higher in patients with comorbidity (P = 0.007), poor compliance (P < 0.001), and in female caregivers (P = 0.013). Conclusion: Statistically speaking, the caregiver burden in substance use disorders is as severe as other mental disorders. The considerable burden on both groups necessitates serious efforts to minimize its negative effects., Competing Interests: None., (Copyright © 2023 Tehran University of Medical Sciences.)

Objective: The addiction pattern of smartphone usage has increased concerns about potential complications. The Smartphone Addiction Scale (SAS), a self-administered questionnaire, evaluates smartphone usage and dependency. The study's purpose was to translate and culturally adapt the SAS short-version into the Persian language (SAS-SV-Pr), and evaluate its psychometric properties. Method : The SAS-SV translation used standardized procedures that involved double-forward and backward translations. A convenience sample, from three medical universities in the city of Teheran (n = 250 students), was recruited to complete the SAS-SV and the Internet Addiction Test (IAT). The content validity index (CVI) and the floor and ceiling effect were considered to evaluate content validity. To evaluate internal consistency and test-retest reliability, Cronbach's Alpha and the Intra-class Correlation Coefficient (ICC2.1) were utilized respectively. Criterion validity was measured by calculating Pearson's correlation coefficient for the total scores of SAS-SV-Pr and IAT (Pearson's r correlation coefficient). Construct validity was evaluated using exploratory factor analysis (EFA) and ratified with confirmatory factor analysis (CFA). Results: During translation and cultural adaptation, only minor wording changes were performed. The correlation between the SAS-SV-Pr and IAT was good (r = 0.57), which determined validity. There was high internal consistency (α = 0.88), split-half reliability (0.84), composite reliability (CR) (0.78) and test-retest reliability (ICC (2.1) = 0.89). Subsequent EFA demonstrated an ambiguous factor structure, being border-line between one- and two-factors, which explained 50.28% of total variance. The CFA confirmed that the two-factor solution was preferred. Our data did not show floor or ceiling effects. Conclusion: The Persian SAS-SV is a two-factor structure outcome measure to evaluate the dependency of smartphone users. It has demonstrated satisfactory psychometric properties for validity, reliability and factor structure, and is suitable for screening and research aims among Persian subjects., Competing Interests: None., (Copyright © 2023 Tehran University of Medical Sciences.)

Objectives: Applying technologies such as virtual reality (VR) in education has gained popularity especially in comprehending abstract and subjective phenomena. Previous studies have shown that applying a virtual reality simulation of psychosis (VRSP) is useful in increasing knowledge and empathy toward patients. Here, the efficacy of using VRSP in altering stigma, empathy and knowledge as well as side effects have been assessed in medical students in comparison with the routine education (visiting the patients)., Method: After attending one session of lecture about positive psychotic symptoms, medical students were allocated to two groups: experiencing one session of VRSP or visiting patients under supervision as routine practice in the ward. Before and after the first session and after the second one, questionnaires of knowledge, empathy and stigma were filled by students. Finally, the results were compared in two groups., Results: Both interventions were effective in reducing stigma as well as increasing knowledge and empathy toward patients with psychotic experiences. VRSP could significantly reduce stigma and increase knowledge and empathy compared with the traditional visiting patients under supervision. The side effects were minimal and ameliorated right after the experience., Conclusion: VRSP is an effective tool in decreasing stigma and increasing empathy and knowledge of the students and can be incorporated in psychiatric education with minimal side effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zare-Bidaki, Ehteshampour, Reisaliakbarighomi, Mazinani, Khodaie Ardakani, Mirabzadeh, Alikhani, Noroozi, Momeni, Samani, Mehrabi Tavana, Esmaeili and Mousavi.)

Background: Despite many efforts, Iran continues to have a high rate of traffic accidents and poor health outcomes. This study aimed to measure income-related inequality for traffic accident health outcomes in Iran, a country with one of the highest rates of traffic accidents and related health problems., Methods: The source of data was a national representative survey named the Iranian Multiple Indicator Demographic and Health Survey (IrMIDHS, 2010). Monthly household income is obtained through self-report in different quarters. Disparity rate ratio (DRR), slop index of inequality (SII) and the population attributable risk percentage measure (PAR%) were calculated. The concentration index (CI) of RTIs was used as our measure of socioeconomic inequality and decomposed into its determining factors., Results: Using the DRR index, in the lowest income group, the risk of death from an accident was 2.3 times, greater and the risk of accidental disability was 11.7 times greater than for the third income quartet. The slope index also shows that the rate of road traffic deaths, disability and injury per 100,000 individuals decreased by 28, 82, and 392 moving from lower to higher incomes. This decrease in injury was about 581 for motorcyclists. CI was -0.04078643 (SE=.01424828, P- value 0.004). Male sex (68.9%), 15-29 yr old age (9.4%), employed activity status (20.8%) has a positive contribution in the RTIs concentration index., Conclusion: In addition to intervention related to the road safety and vehicles and reducing human errors, prevention of the road traffic ill health outcomes requires attention to reduction of inequality in society., Competing Interests: Conflict of interests The authors declare that they have no competing interests., (Copyright © Iranian Public Health Association & Tehran University of Medical Sciences.)

Determining depression symptoms in schizophrenic patients is a challenging process because of a degree of similarity between depression symptoms and negative symptoms and the extrapyramidal side effects of neuroleptic drugs, but it is crucial to evaluate and measure depression among patients with schizophrenia for a better clinical outcome. The Calgary Depression Scale for Schizophrenia (CDSS) is a valid and reliable instrument used for the evaluation of depression in schizophrenia. This study aimed to determine the psychometric properties of the Persian version of CDSS in a sample of people with schizophrenia. Clinical interviews were conducted with 95 schizophrenic patients (40 inpatients and 55 outpatients), who were assessed with the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HDRS-17 and HDRS-24 items), and the Calgary Depression Rating Scale (CDSS). Then an exploratory factor analysis was conducted to determine correlations between scales, Cronbach's alpha, and cutoff scores. The factor analysis led to the extraction of a unifactorial solution. The CDSS had significant relationships with PANSS Negative and PANSS General. However, it had no significant relationship with PANSS Positive and the PANSS Total. The CDSS also had significant relationships with HDRS-17 and HDRS-24. In addition, Cronbach's alpha of total score, test-retest reliability, and cutoff score were estimated at 0.86, 0.82, and 8 (sensitivity = 0.79 and specificity = 0.84), respectively. The findings support the CDSS unifactorial approach. Results also showed that the CDSS Persian version had acceptable psychometric properties; thus, it could be employed to evaluate depression among schizophrenic patients., (Copyright © 2019. Published by Elsevier B.V.)

Background: Responsiveness as a nonmedical, nonfinancial aspect of a health system's goals requires special attention, particularly in people with physical disabilities. This study aimed to investigate the predictors of poor responsiveness of rehabilitation centers in Tehran. Methods: A cross sectional study was conducted to investigate 610 individuals with physical disabilities who referred to 10 comprehensive rehabilitation centers in Tehran using Quota sampling in 2016-2017. The following questionnaires were used in this study: Health System Responsiveness questionnaire, recommended by World Health Organization (WHO); Activities of Daily Living (ADL); and Instrumental Activity of Daily Living (IADL). Multiple logistic regression models were used to determine the sociodemographic characteristics (sex, age, perceived social class, etc.), self-assessed health, and physical functioning [(eg, Instrumental Activities of Daily Living (IADL)] as predictors of poor responsiveness in comprehensive rehabilitation centers of Tehran. Results: The mean years of education of respondents was 12.57 (SD=5.07). The majority of the participants perceived themselves as belonging to the middle class. Among the participants, 17.1% were completely dependent in their instrumental activities of daily living (IADL). Respondents who were not satisfied with their health insurance accounted for 40.2% of the sample. Also, 20.9% of the participants reported poor responsiveness. Based on the logistic regression model, variables of education, perceived social class, satisfaction with health insurance, and IADL were predictors of overall poor responsiveness after adjusting other covariates. Conclusion: Level of education was a strong predictor of poor responsiveness. Insurance companies should make policies to facilitate people's access to rehabilitation services and increase customer satisfaction. Moreover, rehabilitation service providers should pay special attention to those with physical disabilities who are more severely disadvantaged.

In outbred Western populations, most individuals with intellectual disability (ID) are sporadic cases, dominant de novo mutations (DNM) are frequent, and autosomal recessive ID (ARID) is very rare. Because of the high rate of parental consanguinity, which raises the risk for ARID and other recessive disorders, the prevalence of ID is significantly higher in near- and middle-east countries. Indeed, homozygosity mapping and sequencing in consanguineous families have already identified a plethora of ARID genes, but because of the design of these studies, DNMs could not be systematically assessed, and the proportion of cases that are potentially preventable by avoiding consanguineous marriages or through carrier testing is hitherto unknown. This prompted us to perform whole-exome sequencing in 100 sporadic ID patients from Iran and their healthy consanguineous parents. In 61 patients, we identified apparently causative changes in known ID genes. Of these, 44 were homozygous recessive and 17 dominant DNMs. Assuming that the DNM rate is stable, these results suggest that parental consanguinity raises the ID risk about 3.6-fold, and about 4.1 to 4.25-fold for children of first-cousin unions. These results do not rhyme with recent opinions that consanguinity-related health risks are generally small and have been "overstated" in the past., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To determine the prevalence and socio-economic disparity among victims with disabilities caused by RTAs in Iran as country with a high rate of accidents., Method: The source of data was the Iranian Multiple Indicator Demographic and Health Survey, a nationwide cross-sectional study. The sampling framework was based on the population and housing census for Iran in 2006. Provincial samples ranged from 400 to 6,400 households. The target sample was 3,096 clusters consisting of 2,187 urban and 909 rural clusters. In the present study, all but a few indicators are reported at provincial levels. Mortality indicators, accident and disability rates, low birth weight rate and young age at marriage rates are presented at the national level only. Logistic regression was performed to investigate the individual and family factors influencing RTAs that lead to disability in Iran., Results: The period prevalence (12 months) of road traffic accident disabilities (RTADs) in the total population of 111415 was 30.52 (95% CI: 21.13.41.64) per 100,000 individuals. Among those who had been injured during the year leading up to the study, the proportion of disabilities caused by RTAs was 31.67 (95% CI; 8.51.54.97) per 1000 pedestrians, 20.99 (95% CI: 13.37.30.75) per 1000 motorcyclists, 18.64 (95% CI: 7.71.29.57) per 1000 vehicle drivers. Multivariate logistic regression analysis showed that the risk of RTADs differed significantly in relation to age (AOR 50-59 vs. 0-9=10. 78, p -value:0.05); activity status (AOR unemployed vs. employed=4.72, p -value:0.001) and family income (AOR q2 vs. q1=0.37, p -value:0.048) of the victim., Conclusion: In addition to the risks associated with socio-economic groups, particularly vulnerable groups, RTADs have consequences which can lead to further marginalization of individuals, can affect their quality of life and damage the community as a whole., Competing Interests: None declared.

Background: Responsiveness as a non-medical, non-financial goal of the health system is of special importance to people with physical disability. The current study assessed the experiences of people with physical disabilities when they encounter rehabilitation centers in Tehran. Methods: This cross-sectional study was conducted in Tehran, the capital of Iran. The sample consisted of 610 people with physical disabilities referred to 10 comprehensive rehabilitation centers (CRCs) selected by Quota sampling. Data were collected by a standard responsiveness questionnaire proposed by the World Health Organization (WHO) and were analyzed by a standard protocol. Blinder-Oaxaca analysis was done to explain the inequality in performance of public and private sectors. Results: Study participants included 298 (48.7%) women and 312 (51.3%) men. The mean age of the respondents was 46.3 ( SD = 14.3) for women and 45.6 ( SD = 15.4) for men. Prompt attention (33.3%) and confidentiality (1.3%) were the most and least important reported domains, respectively. Overall poor responsiveness was reported by 20.9% of respondents. Private rehabilitation centers showed significantly better performance in communication, basic amenities and autonomy compared to public centers ( P ≤ 0.05). Perceived social class explained 76% of the inequality in autonomy in the private and public sector ( P ≤ 0.05). Conclusion: Improving overall responsiveness in domains that are of high importance from the respondents' viewpoint but are performing poorly-areas such as prompt attention and basic amenities-is essential. Additionally, interventions are needed to improve the performance of the public centers and providers in the areas of participation of service users in all social classes in their rehabilitation decisions and procedures, clear communication, and basic amenities.

There have been few studies of pregnenolone therapy in schizophrenia and those that exist have been subject to several critical limitations, thus yielding inconsistent results. We attempted to assess the therapeutic effect of pregnenolone in a patient sample as homogeneous as possible. In this randomized double-blind clinical trial, 82 female inpatients with chronic schizophrenia, who had discontinued their antipsychotic medications for at least one week in case of any oral antipsychotic medication or a month for any depot antipsychotic medication, received risperidone plus either pregnenolone (50 mg/day) or placebo for 8 weeks. Inclusion criteria were acute illness with a baseline Positive and Negative Syndrome Scale (PANSS) negative subscale score of ≥20. Exclusion criteria were the presence of severe depression or other concomitant psychiatric disorders. Primary outcome was defined as the difference in the PANSS total score change from baseline to week 8 in the pregnenolone group compared to the placebo group. No significant difference was found in the PANSS total score changes between the two arms (mean difference (CI 95%) = -9.41 (-20.24 to 1.41); p = 0.087). Significant differences were initially found for PANSS negative change scores (mean difference (CI 95%) = -2.61 (-5.03 to -0.19); p = 0.035) and general psychopathology change scores (mean difference (CI 95%) = -5.93 (-11.37 to -0.48); p = 0.033). However, these findings did not survive Bonferroni correction for multiple testing. While this trial may suggest a potential effect of pregnenolone on schizophrenia symptoms, further studies are warranted., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Recent evidences suggest that glutamatergic dysregulation implicated in neural plasticity and cellular resilience may contribute to the pathophysiology of Major Depressive Disorder (MDD). Riluzole, which exerts its effect by targeting glutamate neurotransmission, has shown antidepressant effect in recent preclinical, observational and open label studies. This study aimed to assess the efficacy and tolerability of riluzole in patients with MDD. Sixty-four inpatients with diagnosis of moderate to severe major depressive disorder participated in a parallel, randomized, controlled trial, and sixty patients underwent 6 weeks treatment with either riluzole (50 mg/bid) plus citalopram (40 mg/day) or placebo plus citalopram (40 mg/day). All participants were inpatients for the whole duration of the study. Patients were assessed using Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4 and 6. The primary outcome measure was to assess the efficacy of riluzole compared to placebo in improving the depressive symptoms. General linear model repeated measures demonstrated significant effect for time × treatment interaction on HDRS [F (1.86, 107.82) = 8.63, p < 0.001]. Significantly greater improvement was observed in HDRS scores in the riluzole group compared to the placebo group from baseline HDRS score at weeks 2, 4 and 6 (p < 0.001, p = 0.001, p = 0.002, respectively). Significantly greater response with greater speed to treatment was observed in the riluzole group than the placebo group. No serious adverse event occurred. This study showed a favorable safety and efficacy profile in patients with major depressive disorder. Larger controlled studies with longer treatment periods are needed to investigate long term safety, efficacy and optimal dosing., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: The evident central role of inflammation, oxidative stress, and metabolic derangement in pathophysiology of negative symptoms of schizophrenia has opened new insights into probable pharmacological options for these symptoms. Pioglitazone is an antidiabetic agent with anti-inflammatory and antioxidant properties. In this study, we evaluated the efficacy of pioglitazone as an adjunct to risperidone for reduction of negative symptoms in schizophrenia., Methods: In this randomized, double-blind, placebo-controlled trial, 40 patients with chronic schizophrenia and a minimum score of 20 on the negative subscale of Positive and Negative Syndrome Scale (PANSS) were randomly allocated to receive risperidone plus either pioglitazone (30 mg/day) or placebo for 8 weeks. Patients' symptoms and adverse events were rated at baseline and weeks 2, 4, 6, and 8. The difference between the two groups in decline of PANSS negative subscale scores was considered as the primary outcome of this study., Results: At the study endpoint, patients in the pioglitazone group showed significantly more improvement in PANSS negative subscale scores (p < 0.001) as well as PANSS total scores (p = 0.01) compared with the placebo group., Conclusion: These findings suggest the probable efficacy of pioglitazone as an augmentation therapy in reducing the negative symptoms of schizophrenia., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Fundamental problems with Personality Disorders (PD) diagnostic system in the previous version of DSM, led to the revision of DSM. Therefore, a multidimensional system has been proposed for diagnosis of personality disorder features in DSM-5. In the dimensional approach of DSM-5, personality disorders diagnosis is based on levels of personality functioning (Criteria A) and personality trait domains (Criteria B)., Objectives: The purpose of this study was firstly, to examine the DSM-5 levels of personality functioning in antisocial and borderline personality disorders, and second, to explore which levels of personality functioning in patients with antisocial and borderline personality disorders can better predicted severity than others., Patients and Methods: This study had a cross sectional design. The participants consisted of 252 individuals with antisocial (n = 122) and borderline personality disorders (n = 130). They were recruited from Tehran prisoners, and clinical psychology and psychiatry centers of Razi and Taleghani Hospitals, Tehran, Iran. The sample was selected based on judgmental sampling. The SCID-II-PQ, SCID-II and DSM-5 levels of personality functioning were used to diagnose and assess personality disorders. The data were analyzed by correlation and multiple regression analysis. All statistical analyses were performed using the SPSS 16 software., Results: Firstly, it was found that DSM-5 levels of personality functioning have a strong correlation with antisocial and borderline personality symptoms, specially intimacy and self-directedness (P < 0.001). Secondly, the findings showed that identity, intimacy and self-directedness significantly predicted antisocial personality disorder severity (P < 0.0001). The results showed that intimacy and empathy were good predictors of borderline personality disorder severity, as well (P < 0.0001)., Conclusions: Overall, our findings showed that levels of personality functioning are a significant predictor of personality disorders severity. The results partially confirm existing studies.

Selective estrogen receptor modulators (SERMs) such as raloxifene have already shown beneficial effects on negative, positive and general psychopathology symptoms in postmenopausal women with schizophrenia. The purpose of the present investigation was to assess the efficacy of raloxifene as an adjuvant agent in the treatment of men with chronic schizophrenia in an 8-week double-blind and placebo-controlled trial. In a randomized, double-blind and placebo-controlled study, forty-six male patients diagnosed with schizophrenia (DSM-IV-TR), were randomized to either raloxifene (120 mg/day) or placebo in addition to risperidone (6 mg/day) for eight weeks. The assessment was performed using the positive and negative symptom scale (PANSS) at baseline, and at weeks 2, 4, 6 and 8. Extrapyramidal symptom rating scale (ESRS) at baseline, weeks 1, 2, 4, 6, 8 and Hamilton depression rating scale (HDRS) at baseline and week 8 were also used to assess extrapyramidal symptoms and depression simultaneously. Forty-two patients completed the trial. The raloxifene group showed significantly greater improvement on the negative subscale (P<0.001), the general psychopathology subscale (P=0.002) and total PANSS score (P<0.001) in comparison to the placebo group at the endpoint. There was no significant difference in the reduction of positive symptoms score between the two group (P=0.525). Extrapyramidal symptom rating scale and Hamilton depression rating scale and frequency of other adverse effects were comparable between two groups.This study indicates raloxifene as a potential adjunctive treatment strategy for chronic schizophrenia in men.

The objective of this study was to assess the efficacy and tolerability of minocycline add-on to risperidone in treatment of negative symptoms of patients with chronic schizophrenia. In a randomized double-blind placebo-controlled study, 40 patients with chronic schizophrenia who were stabilized on risperidone for a minimum duration of eight weeks were recruited. The patients were randomly assigned to minocycline (titrated up to 200 mg/day) or placebo in addition to risperidone (maximum dose of 6 mg/day) for eight weeks. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, and Extrapyramidal Syndrome Rating Scale were used. Thirty-eight patients completed the study. Significant time × treatment interaction for negative [F(2.254,85.638)=59.046, P<0.001] general psychopathology [F(1.703,64.700)=6.819, P=0.001], and positive subscales [F(1.655,62.878)=5.193, P=0.012] as well as total PANSS scores [F(1.677,63.720)=28.420, P<0.001] were observed. The strongest predictors for change in negative symptoms were the treatment group (β=-0.94, t=-10.59, P<0.001) followed by the change in PANSS positive subscale (β=-0.185, t=-2.075, P=0.045). Side effect profiles of the two treatment regimens were not significantly different. Minocycline seems to be an efficacious and tolerable short-term add-on to risperidone for treatment of negative and general psychopathology symptoms of schizophrenia., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Rationale: Several recent studies have focused on glutamate modulating agents for symptoms relief in schizophrenia, especially negative symptoms which are resistant to conventional therapies., Objectives: We aimed to assess the efficacy and tolerability of riluzole, an anti-glutamate agent with neuroprotective properties, as an adjunct to risperidone in improving negative symptoms of schizophrenia., Methods: In this randomized double-blind placebo-controlled parallel-group study, 50 patients with chronic schizophrenia and a score of ≥20 on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. Participants were equally randomized to receive riluzole (100 mg/day) or placebo in addition to risperidone (up to 6 mg/day) for 8 weeks. Participants were rated by PANSS every 2 weeks. The primary outcome of this study was the difference in the decrease of PANSS negative subscale score from baseline to the study endpoint between the two groups., Results: By the study endpoint, riluzole-treated patients showed significantly greater improvement in the negative symptoms (P < 0.001) as well as the PANSS total and general psychopathology subscale scores (P = 0.001 and P < 0.001; respectively) compared to the placebo group. Treatment group was the only significant predictor of changes in negative symptom in this trial (β = -0.56, P < 0.001). No significant difference was observed between two groups in the frequency of side effects., Conclusion: These preliminary findings suggest that riluzole may be a safe and effective medication for the treatment of negative symptoms in patients with chronic schizophrenia. Further research and replication of study findings is warranted. Clinical trial registry name and registration number: Iranian registry of clinical trials www.irct.ir , IRCT201107281556N26

Objectives: Despite the burden of negative symptoms on quality of life in schizophrenic patients, no completely effective treatment has been developed to address such symptoms yet. Abnormalities in oxidative stress pathways have been recently demonstrated to be involved in the pathophysiology of schizophrenia, and a growing interest in antioxidant agents is emerging for targeting negative symptoms of schizophrenia. N-Acetylcysteine (NAC) is a potent antioxidant with neuroprotective properties. This study aimed to evaluate the possible effects of NAC as an adjunct to risperidone in treating negative symptoms of schizophrenia., Materials and Methods: In this randomized, double-blind, placebo-controlled, parallel-group study, 42 patients with chronic schizophrenia and a score of 20 or greater on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. The participants were equally randomized to receive NAC (up to 2 g/d) or placebo, in addition to risperidone (up to 6 mg/d) for 8 weeks. The participants were rated using PANSS every 2 weeks, and the decrease of PANSS negative subscale score was considered as our primary outcome., Results: By the study end point, NAC-treated patients showed significantly greater improvement in the PANSS total (P = 0.006) and negative subscale (P < 0.001) scores than that in the placebo group, but this difference was not significant for positive and general psychopathology subscales. There was no significant difference between the 2 groups in the frequency of adverse effects., Conclusions: NAC add-on therapy showed to be a safe and effective augmentative strategy for alleviating negative symptoms of schizophrenia.

Rational: A growing body of evidence illustrates that 5-HT3 receptor antagonist drugs may be of benefit in the treatment of negative symptoms in schizophrenia., Objective: The objective of this study was to assess the efficacy and tolerability of tropisetron add-on to risperidone on negative symptoms in patients with chronic stable schizophrenia., Methods: In a double-blind, placebo-controlled 8-week trial, 40 patients with chronic schizophrenia who were stabilized on risperidone were randomized into tropisetron or placebo add-on groups. Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) every 2 weeks. Furthermore, extrapyramidal and depressive symptoms as well as side effects were assessed. The primary outcome measure was the difference in change from baseline of negative subscale scores between the two groups at week 8., Results: Tropisetron resulted in greater improvement of the total PANSS scores [F(1.860,70.699) = 37.366, p < 0.001] as well as negative scores [F(2.439,92.675) = 16.623, p < 0.001] and general psychopathology [F(1.767,67.158) = 4.602, p = 0.017], but not positive subscale scores [F(1.348, 51.218) = 0.048, p = 0.893] compared to placebo. In a multiple regression analysis controlling for positive, extrapyramidal, and depressive symptoms, treatment group (standardized β = -0.640) significantly predicted changes in primary negative symptoms. The side effect profile did not differ significantly between the two groups., Conclusion: Tropisetron add-on to risperidone improves the primary negative symptoms of patients with chronic stable schizophrenia.

Some 5-HT3 antagonists such as ondansetron have shown beneficial effects on negative symptoms of patients with schizophrenia. We aimed to evaluate the efficacy of granisetron (another 5-HT3 antagonist) add-on therapy in the treatment of negative symptoms of patients with stable schizophrenia. In a randomized, double-blind, and placebo-controlled study, forty stable patients with schizophrenia (DSM-IV-TR), were randomized to either granisetron (1 mg twice daily) or placebo (twice daily) in addition to risperidone up to 6 mg/day for eight weeks. The patients were assessed using positive and negative syndrome scale (PANSS) and extrapyramidal symptom rating scale (ESRS) at baseline, week 4 and 8. Hamilton depression rating scale (HDRS) was used to assess depression at baseline and week 8. Thirty-eight patients completed the trial. Granisetron group showed a significantly greater improvement on negative subscale than the placebo group at endpoint [t(38) = 6.046, mean difference (±95% CI) = 3.2(1.8-3.7), P < 0.001]. The same effect was observed for total score [t(38) = 4.168, mean difference (95% CI) = 3.2(1.6-4.7), P < 0.001]. However the placebo and granisetron groups did not differ in their reduction of positive and general psychopathology symptoms scores. HDRS scores and its changes did not differ between the two groups. The ESRS score at week 4 was significantly lower in the granisetron than the placebo group while the two groups showed similar ESRS score at week 8. Frequency of other side effects was similar between the two groups. In summary, granisetron add-on can safely and effectively reduce the primary negative symptoms of patients with schizophrenia., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Cardiovascular disease is an important cause among natural causes of death in schizophrenic patients. The metabolic syndrome (MetS) has been associated with an increased risk of morbidity and mortality due to cardiovascular disease. There are limited if any data on prevalence of MetS in Iranian patients with schizophrenia., Methods: Between December 2007 and May 2008, all consecutive patients with schizophrenia hospitalized at our university psychiatry hospital were entered in the study. The prevalence of MetS was evaluated based on the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP-III), the adapted ATP-III guidelines (ATP-III A), and the recently suggested criteria by International Diabetes Federation (IDF)., Results: Of the study participants, 223 were men (59.9%) and 149 women (40.1%). Overall prevalence of the MetS according to the different definitions were 27.4% (ATP-III), 37.6% (ATP-III A), and 38.7% (IDF), which was over 30% more than the prevalence of MetS in the Iranian general population. The MetS was much more prevalent in women which mainly related to the fact that women had central obesity more frequently., Conclusions: Our results confirm the high prevalence of MetS in schizophrenic patients. These results clearly suggest the necessity for a careful monitoring and management of metabolic risk factors in this high-risk population.

Impaired activity of the purinergic system is a plausible common factor that could be responsible for many aspects of schizophrenia. Based on purinegic hypothesis of schizophrenia, pharmacological treatments enhancing adenosine activity could be effective treatment in schizophrenia. Propentofylline is a novel xantine derivative which is being developed for treatment of degenerative and vascular dementia. It enhances extracellular adenosine level via inhibition of adenosine uptake. The purpose of the present investigation was to assess the efficacy of propentofylline as an adjuvant agent in the treatment of chronic schizophrenia in an 8-week double blind and placebo controlled trial. Eligible participants in this study were 50 patients with chronic schizophrenia. All patients were inpatients and were in the active phase of the illness, and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion, 25 to risperidone 6 mg/day plus propentofylline 900 mg/day (300 mg TDS) and 25 to risperidone 6 mg/day plus placebo. The principal measure of the outcome was Positive and Negative Syndrome Scale (PANSS). Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of risperidone and propentofylline showed a significant superiority over risperidone alone in the treatment of positive symptoms, general psychopathology symptoms as well as PANSS total scores. The means Extrapyramidal Symptoms Rating Scale for the placebo group were higher than in the propentofylline group over the trial. However, the differences were not significant. The present study indicates propentofylline as a potential adjunctive treatment strategy for chronic schizophrenia. Nevertheless, results of larger controlled trials are needed, before recommendation for a broad clinical application can be made.

Objective: It has been reported that selegiline, a Selective Monoamine Oxidase Inhibitor B (MAOI-B), at low doses would be helpful for treating negative symptoms in schizophrenia. Nevertheless, the results are contradictory so far. This study was designed to investigate the effect of selegiline added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in an 8 week, double blind and randomized clinical trial., Methods: Eligible participants in this study were 40 patients with chronic schizophrenia. All patients were inpatients and were in the active phase of the illness, and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion, 20 to risperidone 6 mg/day plus selegiline 10 mg/day (5 mg bid) and 20 to risperidone 6 mg/day plus placebo. The principal measure of the outcome was Positive and Negative Syndrome Scale (PANSS)., Results: Although both protocols significantly decreased the score of the positive, negative, and general psychopathological symptoms over the trial period, the combination of risperidone and selegiline showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores., Conclusion: The present study indicates selegiline as a potential adjunctive treatment strategy for the negative symptoms of schizophrenia. Nevertheless, results of larger controlled trials are needed before recommendation for a broad clinical application can be made., ((c) 2007 John Wiley & Sons, Ltd.)