Usefulness of the University of California San Diego Performance-Based Skills Assessment for the evaluation of cognitive function and activities of daily living function in patients with cognitive impairment.

OBJECTIVES: To assess the usefulness of the University of California San Diego Performance-Based Skills Assessment (UPSA) as a new diagnostic method and tool for the assessment of cognitive function and activities of daily living function in patients with cognitive impairment. METHOD: In total, 35 patients with cognitive impairment and 35 healthy controls were recruited for this study. The Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS) were used for the evaluation of cognitive function, while the Barthel Activities of Daily Living Index (BADL), Instrumental Activities of Daily Living Index (IADL), and UPSA were used for the evaluation of activities of daily living function. RESULTS: UPSA scores were significantly lower in patients with cognitive impairment than in controls. The UPSA total score was significantly correlated with MMSE, CDR, GDS, and IADL scores. With regard to the detection of cognitive impairment, UPSA exhibited a greater determination power (R2 = 0.593) compared with BADL (R2 = 0.149) and IADL (R2 = 0.423) and higher sensitivity and specificity compared with IADL. CONCLUSION: Our results suggest that UPSA is a useful tool for the evaluation of cognitive function and activities of daily living function in patients with cognitive impairment.

Differences in cognitive function and daily living skills between early- and late-stage schizophrenia.

OBJECTIVES: Cognitive dysfunction is a core feature of schizophrenia; deficits often manifest prior to diagnosis and persist throughout the course of the illness. This study was performed to assess the difference in cognitive function and daily living skills between the early- and late-stage schizophrenia. METHODS: Fifty-five clinically stable patients with schizophrenia were recruited (25 with < 5-year and 30 with > 5-year disease durations). We evaluated subjects' clinical states, cognitive function, and psychosocial factors. The Korean versions of MATRICS Consensus Cognitive Battery and UCSD Performance-based Skills Assessment were used for evaluating cognitive function and daily living skills. Chi-square, Wilcoxon rank sum, and t-tests were used to analyze the data. RESULTS: The two groups did not differ for most demographic variables. No significant differences between groups were found for clinical symptoms, psychosocial factors, or non-social cognitive domains. However, the early-stage group had higher social cognition domain scores than the late-stage group (p = 0.01). Early-stage patients scored significantly higher than those in the late-stage group did in the communication and comprehension/planning domains (p = 0.037 and 0.027, respectively), and total score (p = 0.003) of the Performance-based Skills Assessment. CONCLUSIONS: We observed significant differences between patients with early- and late-stage illness with regard to social cognition and performance-based skills.

Treating symptomatic hyperprolactinemia in women with schizophrenia: presentation of the ongoing DAAMSEL clinical trial (Dopamine partial Agonist, Aripiprazole, for the Management of Symptomatic ELevated prolactin).

Prolactin elevations occur in people treated with antipsychotic medications and are often much higher in women than in men. Hyperprolactinemia is known to cause amenorrhea, oligomenorrhea, galactorrhea and gynecomastia in females and is also associated with sexual dysfunction and bone loss. These side effects increase risk of antipsychotic nonadherence and suicide and pose significant problems in the long term management of women with schizophrenia. In this manuscript, we review the literature on prolactin; its physiology, plasma levels, side effects and strategies for treatment. We also present the rationale and protocol for an ongoing clinical trial to treat symptomatic hyperprolactinemia in premenopausal women with schizophrenia. More attention and focus are needed to address these significant side effects and help the field better personalize the treatment of women with schizophrenia.

Bone mineral density and osteoporosis risk in older patients with schizophrenia.

OBJECTIVE: People with schizophrenia are at a higher risk for osteoporosis. The authors investigated the prevalence of low bone density and its risk factors in older Korean patients with schizophrenia. METHOD: In cross-sectional study, 327 inpatients with schizophrenia were screened. Among them, 229 patients older than 50 years participated in this study. The control group consisted of healthy volunteers who were of similar ages (n = 125). Bone density was measured in the lumbar spine and the neck, trochanter, and ward regions of the right proximal femur by dual-energy x-ray absorptiometry. Clinical variables such as alcohol use, cigarette smoking, and fracture history were obtained. The Student t test, Pearson χ2 test, Wilcoxon rank sum test, and logistic regression analysis were used. RESULTS: The prevalence of osteoporosis was significantly higher in patients with schizophrenia compared with healthy controls (34.9% vs 18.4%, P = 0.0043). Within the schizophrenia group, female subjects had a significantly higher prevalence of osteoporosis than male subjects (48.4% vs 25.7%, P = 0.0014); however, no sex differences were identified in the healthy control group. The actual bone density and t scores in patients with schizophrenia were significantly lower in all sites than in healthy controls. Among patients with schizophrenia, smokers and alcohol abuser showed lower bone density compared with those who did not smoke or drink. The lifetime prevalence of fracture was significantly higher in patients with schizophrenia (24.0%) compared with healthy controls (5.6%; P = 0.001). CONCLUSIONS: Our results emphasize that older patients with schizophrenia are at risk for low bone density. Cigarette smoking and alcohol abuse are associated with low bone density in patients with schizophrenia.

Brief report: the effect of suggestion on unpleasant dreams induced by ketamine administration.

The use of ketamine may be associated with the recall of unpleasant dreams after sedation. We hypothesized that a positive suggestion before sedation could reduce the incidence of ketamine-induced unpleasant dreams. To test this hypothesis, we randomized 100 patients receiving sedation with ketamine for their procedure into 2 groups with 1 group having an anesthesiologist provide a mood-elevating suggestion to the patient before ketamine administration (suggestion group), whereas in the control group no suggestion was provided. Patients were provided with a pleasantness/unpleasantness scale to rate "the overall mood of the dream" as very unpleasant (grade 1), quite unpleasant (grade 2), neither or mixed (grade 3), quite pleasant (grade 4), and very pleasant (grade 5). In those patients who lost consciousness, the frequencies of grades 1, 2, 3, 4, and 5 were 0%, 0%, 46%, 24%, and 30% in the suggestion group and were 6%, 2%, 70%, 12%, and 10%, respectively, in the control group (P=0.01). In the intent-to-treat population the overall frequency between groups was very similar. This study implies that when administering ketamine as part of a sedation regimen, positive suggestion may help reduce the recall of unpleasant dreaming.

Developing clinical cut-off scores for the university of California San Diego performance-based skills assessment in patients with schizophrenia.

This study aimed to obtain University of California San Diego Performance-based Skill Assessment (UPSA) cut-off scores for the purpose of severity classification and to expand the clinical utility of the UPSA for the evaluation of cognitive function in patients with schizophrenia. In total, 191 patients with schizophrenia were recruited. The UPSA, Positive and Negative Symptom Scale (PANSS), Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and Global Assessment Functioning Scale (GAF) were used for the evaluation. The cognitive symptoms item of the CGI-SCH was used as a reference and the subjects were divided into three groups: mild, moderate, and severe. The sensitivity and specificity of the UPSA were analyzed by receiver operating characteristic curves. There were significant differences in the UPSA, CGI-SCH, PANSS, and GAF scores among the groups. In the mild and moderate groups, a UPSA score of 59 was identified as the optimal cut-off score, and a score of 41 was identified as the optimal cut-off score in the moderate and severe groups. Severity can be classified using the UPSA score as follows: ≥ 60 for mild, 41-59 for moderate, and ≤ 40 for severe. The UPSA could be used to assess the degree of daily living dysfunction in patients with schizophrenia.

Cardiac-related findings at autopsy in people with severe mental illness treated with clozapine or risperidone.

Clozapine is a superior agent for treatment-refractory patients with schizophrenia, but is underutilized in the US, likely due to the risk of side effects. This study examined all available autopsy data on cardiac disease and risk factors in people with schizophrenia in a sample of deceased persons with severe mental illness who had received clozapine (N=62) or risperidone (N=42). The mean body mass index (BMI) at the time of death was 31.4+/-8.8 kg/m2 and 27.1+/-8.2 kg/m2 in the clozapine and risperidone groups respectively (t=1.98, df=60, p=0.052). Cardiac related measures examined included: abdominal wall thickness, heart weight, left ventricle thickness, right ventricle thickness, presence of notable cardiac involvement (atherosclerosis, fibrosis and hypertrophy) and number of cardiac arteries occluded. No significant differences in any of the cardiac findings were noted between patients in the clozapine and risperidone groups. Independent of treatment, cardiomyopathy deaths were associated with a higher abdominal wall thickness (p=0.042) and a tendency towards higher BMI (p=0.051) as compared to the other causes of death. The results of this study suggest that while clozapine is associated with weight gain and metabolic abnormalities, there does not appear to be an increased occurrence of cardiac abnormalities in deceased persons who were treated with clozapine as compared to risperidone.

The effect of anticholinergic burden on cognitive and daily living functions in patients with schizophrenia.

OBJECTIVE: This study aimed to explore the association between medication-associated anticholinergic burden and cognitive and daily living functions in patients with schizophrenia. METHODS: Sixty patients with schizophrenia were recruited. We used the Anticholinergic Drug Scale (ADS) for evaluating medication-associated anticholinergic burden. The MATRICS Consensus Cognitive Battery (MCCB) and the University of California San Diego Performance-based Skills Assessment (UPSA) were used for evaluating cognitive and daily living functions. To assess clinical symptoms, psychiatrists conducted interviews using the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. RESULTS: Subjects were divided into low (n = 31) and high (n = 29) anticholinergic burden based on ADS scores of 3 or more. The "high ADS" group had poorer cognitive (composite MCCB score, p < 0.001) and daily living functions (total UPSA score, p = 0.001) than the "low ADS" group. Medication-associated anticholinergic burden was negatively correlated with cognitive functions (composite MCCB score, r = -0.512, p < 0.001) and daily living functions (total UPSA score, r = -0.355, p = 0.005). A regression analysis showed that anticholinergic burden significantly explained the decline in cognitive functions (composite MCCB score, R2 = 0.262, p < 0.001) and daily living functions (total UPSA score, R2 = 0.126, p = 0.005). Explanatory power was reduced after a covariate adjustment, but the effects of the composite MCCB score (p = 0.013) and of the transportation domain score of the UPSA (p = 0.048) remained significant. CONCLUSIONS: Our analysis shows that anticholinergic burden reduces cognitive and daily living functions in patients with schizophrenia. A drug strategy with minimal anticholinergic burden may be helpful to patients if it does not adversely affect clinical symptoms.

Increased Bone Mineral Density after Abstinence in Male Patients with Alcohol Dependence.

OBJECTIVE: This study aimed to compare the bone mineral density of male patients with alcohol dependence with that in healthy controls and to assess changes in bone density after abstinence. METHODS: Forty-four inpatients with confirmed the Diagnostic and Statistical Manual of Mental Disorders, fourth edition diagnosis of alcohol abuse and 42 controls were recruited. Bone density was determined with dual-energy X-ray absorptiometry in the lumbar spine as well as in the femoral neck, trochanter, and Ward's triangle regions of the proximal right femur. RESULTS: There were no significant differences in age and body mass index between patients with alcohol dependence and healthy controls. In the alcohol dependence group, osteopenia and osteoporosis were found in 54.5% and 34.1% of the patients, respectively, whereas in the control group, the corresponding values were 45.2% and 11.9% (p=0.001). Although the actual bone density in the femur and the corresponding T-scores were significantly lower in the alcohol dependence group, no significant differences were found in the lumbar spine. In both groups, body mass index showed a significant correlation with bone mineral density in all areas. After 3 to 4 years of abstinence, bone density significantly increased in the lumbar and femur. CONCLUSION: We conclude that bone mineral density in patients with alcohol dependence was significantly lower than that in healthy controls, and the rates of osteopenia and osteoporosis are higher. Importantly, abstinence from alcohol increases bone density.

Adjunct transcranial direct current stimulation improves cognitive function in patients with schizophrenia: A double-blind 12-week study.

OBJECTIVES: Cognitive impairment is a common symptom of schizophrenia that has significant effects on quality of life and the activities of daily living. The present study examined the ability of transcranial direct current stimulation (tDCS) to improve cognitive function and clinical symptoms in patients with schizophrenia. METHODS: Fifty-six patients with schizophrenia were randomized to real-tDCS and sham-tDCS groups. The participants were stable for a period of 3months before study enrollment. Each group received 30min of active 2-mA tDCS or sham stimulation over the left dorsolateral prefrontal cortex (anode F3, cathode F4) once per day for 10 consecutive weekdays. The Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) and Wisconsin Card Sorting Test (WCST) were used to evaluate cognitive function, and the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia scale (CGI-SCH), and Calgary Depression Scale for Schizophrenia (CDSS) were used to evaluate symptoms at baseline, after 10 sessions, and at 3-month follow-up. RESULTS: There was a significant time×group interaction, indicating that MCCB working memory (P=0.008) and overall scores (P=0.031) improved over time in the real-tDCS group compared to the sham-tDCS group. There was also a significant time×group interaction for depressive symptoms as evaluated by the CGI-SCH, which decreased over time in the real-tDCS group (P=0.041). tDCS treatment combined with antipsychotic medication was generally well-tolerated and safe. CONCLUSIONS: Adjunct tDCS treatment is safe and effective for improving cognitive status in patients with schizophrenia.

Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial.

OBJECTIVE: Hyperprolactinemia and associated side effects often occur with antipsychotics. The authors investigated the effect of adjunctive treatment with aripiprazole on hyperprolactinemia and psychopathology in patients with schizophrenia maintained with haloperidol. METHOD: Fifty-six patients with hyperprolactinemia taking haloperidol were enrolled. Haloperidol dose was fixed; aripiprazole was dosed at 15 mg/day for the first 4 weeks, then 30 mg/day for the following 4 weeks. Serum prolactin, haloperidol, and aripiprazole levels were measured. Symptoms and side effects were assessed with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms, Clinical Global Impression symptom scale, Simpson-Angus Rating Scale, and Barnes Akathisia Rating Scale at weeks 1, 2, 4, 6, and 8. RESULTS: Prolactin levels of patients receiving aripiprazole significantly decreased over time, demonstrating a significant time effect and a time-by-group interaction. In the aripiprazole group, 88.5% of patients at week 8 had prolactin levels normalize compared to 3.6% of patients receiving placebo. Among 11 female patients with menstrual disturbances randomly assigned to aripiprazole, seven patients regained menstruation during the study, whereas none receiving placebo did. Plasma levels of haloperidol were not significantly altered. No significant time effect and time-by-group interactions on BPRS, Scale for the Assessment of Negative Symptoms, and Simpson-Angus Rating Scale scores were noted. CONCLUSIONS: Adjunctive aripiprazole treatment reversed hyperprolactinemia in both sexes, resulting in reinstatement of menstruation in female patients, with no significant effects on psychopathology and extrapyramidal symptoms. Aripiprazole has higher affinity to dopamine D(2) receptors than haloperidol, which is the likely cause of this observation.

The Korean Version of the Schizophrenia Cognition Rating Scale: Reliability and Validity.

OBJECTIVE: This study's aim was to develop and standardize a Korean version (SCoRS-K) of the Schizophrenia Cognition Rating Scale (SCoRS), which is used to evaluate the degree of cognitive dysfunction affecting the everyday functioning of people with schizophrenia. METHODS: Eighty-four schizophrenia patients with stable symptoms who were receiving outpatient treatment and rehabilitation therapy, and 29 demographically matched non-patient controls, participated in the study. Demographic data were collected, and clinical symptoms, cognitive function, and social function were evaluated to verify SCoRS-K's reliability and validity. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale and the Clinical Global Impression-Schizophrenia Scale. Cognitive function was evaluated using a short form of the Korean Wechsler Adult Intelligence Scale and the Wisconsin Card Sorting Test (WCST). Social function was evaluated using the Social and Occupational Functioning Assessment Scale, the Schizophrenia Quality of Life Scale, and the Social Functioning Scale. RESULTS: Data analysis demonstrated SCoRS-K's statistically significant reliability and validity. SCoRS-K has high internal consistency (Cronbach's alpha; patient 0.941, informant 0.905, interviewer 0.964); test-retest reliability [patient 0.428 (p=0.003), informant 0.502 (p<0.001), interviewer 0.602 (p<0.001); and global rating 0.642 (p<0.001)]. The mean scores of subjects were significantly higher than those of the controls (p<0.001), demonstrating SCoRS-K's discriminant validity. Significant correlations between the total scores and global rating score of SCoRS-K and those of the scales and tests listed above (except WCST) support SCoRS-K's concurrent validity. CONCLUSION: SCoRS-K is a useful instrument for evaluating the degree of cognitive dysfunction in Korean schizophrenia patients.

The Korean Version of the University of California San Diego Performance-based Skills Assessment: Reliability and Validity.

OBJECTIVE: The study's aim was to develop and standardize a Korean version of the University of California San Diego Performance-based Skills Assessment (K-UPSA), which is used to evaluate the daily living function of patients with schizophrenia. METHODS: Study participants were 78 patients with schizophrenia and 27 demographically matched healthy controls. We evaluated the clinical states and cognitive functions to verify K-UPSA's reliability and validity. For clinical states, the Positive and Negative Syndrome Scale, Clinical Global Impression-Schizophrenia scale, and Social and Occupational Functioning Assessment Scale and Schizophrenia Quality of Life Scale-fourth revision were used. The Schizophrenia Cognition Rating Scale, Short-form of Korean-Wechsler Adult Intelligence Scale, and Wisconsin Card Sorting Test were used to assess cognitive function. RESULTS: The K-UPSA had statistically significant reliability and validity. The K-UPSA has high internal consistency (Cronbach's alpha, 0.837) and test-retest reliability (intra-class correlation coefficient, 0.381-0.792; p＜0.001). The K-UPSA had significant discriminant validity (p＜0.001). Significant correlations between the K-UPSA's scores and most of the scales and tests listed above demonstrated K-UPSA's concurrent validity (p＜0.001). CONCLUSION: The K-UPSA is useful to evaluate the daily living function in Korean patients with schizophrenia.

Prevalence of bone mineral density loss in Korean patients with schizophrenia: a cross-sectional study.

OBJECTIVE: This study investigates bone mineral density (BMD) and the association between BMD and hormonal changes in Korean patients with schizophrenia. METHOD: This cross-sectional study was conducted from January 2005 to June 2005; 195 inpatients with schizophrenia (DSM-IV) were screened. Among them, 51 patients aged 18 to 45 years who had taken haloperidol monotherapy for at least 2 years participated in this study. The control group consisted of normal healthy volunteers who were of similar ages (N = 57). Bone mineral density was determined by a GE Lunar 4500 scanner. Hormone levels were measured by using commercial kits. The Student t test, the Pearson chi2 test, the Wilcoxon rank sum test, and logistic regression analysis were used for data analysis. RESULTS: Female patients, but not male patients, showed significantly lower BMD than the normal controls as seen in all bone regions studied. Among 18 female patients with BMD loss, 17 patients showed hyperprolactinemia, and 7 showed combined hypoestrogenemia. Prolactin levels were significantly higher in the female patients with BMD loss compared to those with normal bone density; however, other hormone levels were not different between the 2 groups. There was no significant difference in hormonal levels between bone loss and normal bone density groups. CONCLUSIONS: Bone mineral density loss in patients with schizophrenia tended to differ by gender. Decreased BMD compared to normal controls was seen in female patients; however, this was not observed in men.

Adjunctive varenicline treatment for smoking reduction in patients with schizophrenia: A randomized double-blind placebo-controlled trial.

OBJECTIVES: Smoking is more common among patients with schizophrenia than it is in the general population. Varenicline, a partial and full agonist at the α4ß2 and α7 nicotine acetylcholine receptors, respectively, has been shown to be an effective anti-smoking treatment. This study examined the effects of varenicline treatment on smoking reduction in patients with schizophrenia. METHODS: Sixty smokers with schizophrenia were recruited and randomized to receive either varenicline or placebo. Smoking behavior was assessed with the Minnesota Nicotine Withdrawal Scale (mNWS), Brief Questionnaire of Smoking Urge (QSU-brief), and Modified Cigarette Evaluation Questionnaire (mCEQ). Exhaled carbon monoxide was also measured to assess smoking dependency and status. Data were analyzed with the two-tailed Student's t-test, χ(2) test, and repeated measures ANOVA. RESULTS: During the 8-week study, there was a significant time×group interaction, which showed that smoking decreased over time in the varenicline group. Expired CO levels also decreased in the varenicline group, showing a significant time effect, group effect, and time×group interaction. Total mCEQ scores decreased in the varenicline group, demonstrating a significant time×group interaction. Among the five domains of the mCEQ, the smoking satisfaction, psychological reward, and enjoyment of respiratory tract sensation domains showed significant time×group interactions in the varenicline group. The QSU-brief and mNWS demonstrated a significant time effect, but not significant time×group interactions. Adjunctive varenicline treatment with antipsychotics was generally well-tolerated and safe. CONCLUSIONS: Varenicline showed significant efficacy in reducing smoking in people with schizophrenia.

The Relationship between Language Ability and Cognitive Function in Patients with Schizophrenia.

OBJECTIVE: Cognitive dysfunction is common in people with schizophrenia, and language disability is one of the most notable cognitive deficits. This study assessed the use and comprehension ability of the Korean language in patients with schizophrenia and the correlations between language ability and cognitive function. METHODS: Eighty-six patients with schizophrenia and a group of 29 healthy controls were recruited. We assessed both clinical symptoms and cognitive functions including Korean language ability. For clinical symptoms, the Positive and Negative Syndrome Scale, Clinical Global Impression-Schizophrenia Scale, and Social and Occupational Functioning Assessment Scale were used. For the Korean language ability assessment, a portion of the Korean Broadcasting System (KBS) Korean Language Test was used. The Short-form of Korean-Wechsler Adult Intelligence Scale, the Korean version of the University of California San Diego (UCSD) Performance-based Skills Assessment (K-UPSA), and the Wisconsin Card Sorting Test (WCST) were used to assess cognitive functions. RESULTS: Schizophrenic patients had significantly lower scores in the language and cognitive function tests both in the total and subscale scores. Various clinical scores had negative correlations with reading comprehension ability of the KBS Korean Language Test. The WCST and a part of the K-UPSA had positive correlations with multiple domains of the language test. CONCLUSION: A significant difference was found between schizophrenic patients and controls in language ability. Correlations between Korean language ability and several clinical symptoms and cognitive functions were demonstrated in patients with schizophrenia. Tests of cognitive function had positive correlations with different aspects of language ability.

Lifetime psychiatric symptoms in persons with schizophrenia who died by suicide compared to other means of death.

The focus of this report is to compare the psychiatric symptomatology of individuals with schizophrenia who have died by suicide to those who have died by other means of death. This study includes individuals with a diagnosis of schizophrenia whose families donated their brain tissue to the Maryland Brain Collection between September 1989 and August 1998. The psychological autopsy method was used to assess the deceased individual's demographic and clinical characteristics, psychiatric symptoms and history of suicidal thoughts and attempts. Ninety-seven individuals with schizophrenia were identified for this study. Fifteen had committed suicide, while the remaining 82 died from other causes. Thoughts of suicide and previous suicide attempts were more frequent among the group that died from suicide (93% compared to 26%) (p < 0.0001). Suicide victims had a higher rate of depressive symptoms and were twice as likely to have a depressed mood. The incidence of thoughts of dying was 60% compared to 20% in those who did not commit suicide (p = 0.002). Loss of interest was reported to occur in 20% in the suicide group compared to 4% in the group of individuals that died from other causes (p = 0.05). Victims of suicide also had higher rates of positive symptoms throughout their lifetime including thought control, flight of ideas, and loose associations. Suicide is one of the leading cause of premature death in individuals with schizophrenia and identification of risk factors is of great importance. Individuals who die by suicide experience higher rates of depressive symptoms, suicidal thoughts and positive symptoms during their life.

Long-term effectiveness of flexibly dosed paliperidone extended-release: comparison among patients with schizophrenia switching from risperidone and other antipsychotic agents.

OBJECTIVE: The current study compared the long-term effectiveness, safety, and tolerability of paliperidone extended-release (ER) among patients with schizophrenia who had switched from risperidone (risperidone group) or other antipsychotic medications (non-risperidone group) due to lack of efficacy, intolerability, or non-adherence. RESEARCH DESIGN AND METHODS: This open-label, prospective, multicenter, 48 week study utilized the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity scale (CGI-S), the Personal and Social Performance scale (PSP), and the Subjective Well-being under Neuroleptics scale (SWN) to assess patients with schizophrenia. Additionally, extrapyramidal symptoms (EPS) and subjective side effects were evaluated with validated scales. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00864045. RESULTS: The completion rate for this study was 51.6% (95/184), and 169 patients finished with ≥1 post-baseline assessment (81 patients in the risperidone group, 88 in the non-risperidone group). The mean (SD) PANSS total score decreased significantly from 78.3 (18.8) to 65.5 (19.7) in the risperidone group and from 79.1 (19.8) to 65.4 (20.8) in the other group (all p < 0.001). Similar to PANSS, the severity rating for overall scores of the CGI-S and the PSP scores improved significantly from baseline (all p < 0.001). The magnitude of improvement in all effectiveness measures at 48 weeks did not differ between the two groups. EPS and subjective side effects improved significantly for all patients. Akathisia (18.5%) and increased weight (14.1%) were the main adverse events. Elevated prolactin levels were identified in female subjects in the non-risperidone group. CONCLUSIONS: Switching from previously unsuccessful antipsychotic treatments to paliperidone ER can be a useful option to achieve long-term improvement in symptoms and functioning for patients with schizophrenia. The clinical effectiveness appeared to be similar in patients who previously received risperidone and those treated with other antipsychotic medications. The open-label design and lack of a placebo group were limitations.

Alcohol and cannabis use and mortality in people with schizophrenia and related psychotic disorders.

The impact of co-morbid substance use on mortality is not well studied in psychotic disorders. The objective of this study was to examine the impact of substance use on mortality in people with psychotic disorders and alcohol and/or drug use. We examined the rate of substance use and the risk of substance use on mortality risk over a 4-10 year period in 762 people with psychotic disorders. Deceased patients were identified from the Social Security Death Index and the Maryland Division of Vital Records. Substance use was defined as regular and heavy use or abuse or dependence. Seventy seven percent had co-morbid lifetime substance use, with co-morbid cannabis and alcohol use occurring most commonly. Out of 762 subjects, 62 died during follow up. In a Cox model, predicted mortality risk was higher in age group 35-55 compared to <35 years and in males, but reduced in cannabis users. Overall five- (3.1% vs 7.5%) and ten-year mortality risk (5.5% vs. 13.6%) was lower in cannabis users than in non-users with psychotic disorders (p = 0.005) in a survival model. Alcohol use was not predictive of mortality. We observed a lower mortality risk in cannabis-using psychotic disorder patients compared to cannabis non-users despite subjects having similar symptoms and treatments. Future research is warranted to replicate these findings and to shed light on the anti-inflammatory properties of the endocannabinoid system and its role in decreased mortality in people with psychotic disorders.

Adjunctive varenicline treatment with antipsychotic medications for cognitive impairments in people with schizophrenia: a randomized double-blind placebo-controlled trial.

The aim of this study is to examine the effects of treatment with varenicline, a partial agonist at the α4ß2 and full agonist at the α7 nicotine acetylcholine receptor, on cognitive impairments in people with schizophrenia. In all, 120 clinically stable people with schizophrenia participated in randomized, double-blind, placebo-controlled 8-week trial. Antipsychotic and concomitant medication doses remained fixed throughout the study. Varenicline was titrated up to 1 mg twice daily for weeks 2-8. Neuropsychological, clinical, and safety assessments were administered at baseline and weeks 1, 2, 4, and 8. In the primary analyses of neurocognitive differences at week 8, no varenicline-placebo differences were significant. In secondary longitudinal analyses, varenicline improved compared with placebo on the Digital Symbol Substitution Test (p=0.013) and the Wisconsin Card Sorting Test non-perseverative errors (p=0.043). Some treatment effects were different between smokers and non-smokers. In smokers, Continuous Performance Test hit reaction time (p=0.008) and Stroop Interference (p=0.004) were reduced for varenicline compared with placebo, while there were no treatment differences in non-smokers. No significant treatment main effects or interactions were noted for total scores on the Positive and Negative Syndrome Scale or the Scale for the Assessment for Negative Symptoms. Our findings suggest beneficial effects of adjunctive varenicline treatment with antipsychotics for some cognitive impairments in people with schizophrenia. In some cases, effects of treatment varied between smokers and non-smokers. Further study is required to assess the functional significance of these changes.