Risperidone Group Research Articles

Subjective well-being in schizophrenia: A randomised controlled open-label 12-month non-inferiority study comparing quetiapine XR with risperidone (RECOVER)

This randomised 12-month open study analysed the effectiveness of quetiapine XR (400–800mg) versus risperidone (2–6mg) on subjective well-being in schizophrenia (NCT00600756). Primary objective was to demonstrate non-inferiority of quetiapine XR to risperidone in 6-month responder rate using the Subjective Well-Being under Neuroleptics scale (SWN-K) (per-protocol at Month 6 [PP 6] population). Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) greater than −9.7% for the adjusted difference between quetiapine XR and risperidone. Secondary objectives included non-inferiority of quetiapine XR versus risperidone (lower limit of 95% CI greater than −7.5 points) for SWN-K change from baseline to Month 12 (PP 12). 798 patients were randomised (quetiapine XR, n=395; risperidone, n=403); at Month 12, 212 (54%) and 227 (56%) patients, respectively, completed the study. At Month 6, SWN-K responder rate in the PP 6 population was 65% (136/210) with quetiapine XR and 68% (158/232) with risperidone (adjusted treatment difference: −5.7%; 95% CI: −15.1, 3.7); thus, non-inferiority could not be established. SWN-K change from baseline to Month 12 was 23.2 points for quetiapine XR and 21.1 points for the risperidone group; treatment difference was 2.1 (95% CI: −0.8; 5.0); non-inferiority was established (PP 12). Conclusion: SWN-K response at 6 months was comparable between the two antipsychotics. However, with a lower than expected responder rate and a lower than expected number of evaluable patients in the PP 6 population, non-inferiority was not demonstrated. A secondary objective (SWN-K total score) established non-inferiority of quetiapine XR to risperidone at Month 12.

A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders

BackgroundThis study examined the efficacy and safety of N-acetylcysteine (NAC) augmentation for treating irritability in children and adolescents with autism spectrum disorders (ASD).MethodForty children and adolescents met diagnostic criteria for ASD according to DSM-IV. They were randomly allocated into one of the two groups of NAC (1200 mg/day)+risperidone or placebo+risperidone. NAC and placebo were administered in the form of effervescent and in two divided doses for 8 weeks. Irritability subscale score of Aberrant Behavior Checklist (ABC) was considered as the main outcome measure. Adverse effects were also checked.ResultsThe mean score of irritability in the NAC+risperidone and placebo+risperidone groups at baseline was 13.2(5.3) and 16.7(7.8), respectively. The scores after 8 weeks were 9.7(4.1) and 15.1(7.8), respectively. Repeated measures of ANOVA showed that there was a significant difference between the two groups after 8 weeks. The most common adverse effects in the NAC+risperidone group were constipation (16.1%), increased appetite (16.1%), fatigue (12.9%), nervousness (12.9%), and daytime drowsiness (12.9%). There was no fatal adverse effect.ConclusionsRisperidone plus NAC more than risperidone plus placebo decreased irritability in children and adolescents with ASD. Meanwhile, it did not change the core symptoms of autism. Adverse effects were not common and NAC was generally tolerated well.Trial registrationThis trial was registered at http://www.irct.ir. The registration number of this trial was IRCT201106103930N6

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.

Effects of amisulpride on the cognitive function in first-episode schizophrenia patients

Objective To explore the effects of amisulpride on the cognitive function in first-episode schizophrenia patients. Methods 64 patients in first-episode schizophrenia were divided into two groups randomly according to the method of tossing a coin, then treated with amisulpride or risperidone respectively for 12 weeks.The efficacy and adverse effect were evaluated with positive and negative scale (PANSS) and treatment emergent side effect scale (TESS) before treatment and after treatment for 2 weeks, 4 weeks, 8 weeks, 12 weeks.Before and after treatment for 12 weeks, cognitive function of all the patients was blindly evaluated with Wechsler Scale-revised China (WMS-RC) , Wisconsin Card Sorting Test(WCST)and Trail Making test A and B. Results After 12-week treatment, statistical difference was found in amisulpride(44.7±6.7) and risperidone(45.2±7.4) groups (P 0.05). The cognitive function in first-episode schizophrenia was damaged obviously.In two groups, the scores in recognize, association, comprehend, back a few and MQ of WMS and TAT-A, TAT-B were improved significantly after treatment for 12 weeks(P>0.05). These items of WCST were improved more remarkably than baseline (amisulpride(20.63±13.06), (28.75±15.72), (43.17±22.13), (3.62±2.21), P 0.05). Conclusion The study shows that the cognitive dysfunction in first-episode schizophrenia can be improved by amisulpride, and the efficacy was similar with risperidone. Key words: Amisulpride; Risperidone; Schizophrenia; Cognitive function

Sex differences in the effect of four second‐generation antipsychotics on QTc interval in patients with schizophrenia

We examined sex differences in the effect of olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), or quetiapine (QTP) on mean corrected QT (QTc) intervals among 222 patients with schizophrenia. Subjects were patients with schizophrenia who were treated with either OLZ (n = 69), RIS (n = 60), ARP (n = 62), or QTP (n = 31). Electrocardiographic measurements were conducted, and the QT interval was corrected using Bazett's correction formula. The mean QTc interval of the QTP group was significantly longer than that of the RIS group (p = 0.002) or ARP group (p = 0.029). The mean QTc interval of the OLZ group was also significantly longer than that of the RIS group (p = 0.006). In female participants, the difference in the mean QTc interval among the four second-generation antipsychotic (SGA) groups was statistically significant (p = 0.002), whereas in male patients, there was no significant difference in the mean QTc interval among the four SGA groups. Post hoc analyses showed that sex differences in QTc interval were observed only in OLZ treatment group (p = 0.007). To our knowledge, this is the first study to demonstrate sex differences in the effect of four SGAs on the QTc interval.

Long-term (3-year) neurocognitive effectiveness of antipsychotic medications in first-episode non-affective psychosis: a randomized comparison of haloperidol, olanzapine, and risperidone

The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics is currently under debate. A prospective, randomized, open-label study was carried out to compare the long-term neurocognitive effectiveness of haloperidol, olanzapine, and risperidone in the first episode of schizophrenia spectrum disorders. A final sample of 79 patients randomized to haloperidol (N = 28), olanzapine (N = 23), or risperidone (N = 28) who completed clinical and cognitive evaluations at baseline and 3-year follow-up was included in the final analysis. Forty-one healthy individuals were also included in the final analysis. The main outcome measure was cognitive changes at 3-year follow-up. Due to the fact that some of the patients had switched their initially prescribed antipsychotic medication during the course of the study (6 out of 28 in haloperidol group, 18 out of 23 in olanzapine group, and 24 out of 28 in risperidone group continued with the initial study drug at 3-year assessment), we have also conducted a per protocol analysis. Overall, cognitive changes were similar in the three treatment groups and controls, although a greater improvement in Rey Auditory Verbal Learning Test, Digit Symbol, and Iowa Gambling Test was found in the treatment groups. The better performance observed on Rey Auditory Verbal Learning Test and Digit Symbol in olanzapine treatment group was likely explained by the lower prevalence of use of antimuscarinic drugs. These results were essentially similar to those found in the intention-to-treat analysis. The major conclusion of this study is that haloperidol, olanzapine, and risperidone have not demonstrated substantial neurocognitive effectiveness, improving cognitive deficits present in the early phases of the illness. The study also underscores the importance of exploring new drugs for the treatment of cognitive impairments and associated functional disabilities in schizophrenia.

Differences in plasma prolactin levels in patients with schizophrenia treated on monotherapy with five second-generation antipsychotics

Although second-generation antipsychotics (SGAs) are characterized by fewer prolactin (PRL)-related side effects compared with first-generation antipsychotics, the detailed effects of SGAs on the plasma PRL levels still remain unclear. We examined the differences in plasma PRL levels among 268 patients treated for schizophrenia with olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), quetiapine (QTP), or perospirone (PER). The participants had received antipsychotic monotherapy with stable doses of OLZ, RIS, ARP, QTP, or PER for ≥3weeks, and fasting blood samples were drawn to examine plasma PRL levels. The differences in median plasma PRL levels in all (P<0.001), male (P<0.001) and female patients (P<0.001) among the five SGA groups were statistically significant. A stepwise multiple regression analysis showed that ARP treatment was found to contribute to lower plasma PRL level, while female sex, RIS, OLZ and chlorpromazine equivalent dose were found to contribute to a higher plasma PRL level. The median value of plasma PRL level in the RIS group was twice as much compared with that in the OLZ group, although this was not statistically significant.In this study, OLZ had a considerable effect on plasma PRL level, similar to RIS, while PER did not affect plasma PRL levels, similar to QTP. Further studies are needed to clarify the differences in plasma PRL levels among SGAs.

Cognitive effects of atypical antipsychotic drugs in first-episode drug-naïve schizophrenic patients.

Cognitive impairment is a core feature of schizophrenia. The present randomized open study enrolled antipsychotic-naïve patients who were experiencing their first episode of schizophrenia. After baseline neurocognitive tests and clinical assessment, subjects were randomly assigned to olanzapine, risperidone and aripiprazole treatment groups. A battery of neurocognitive tests showed that risperidone produced cognitive benefits in all five cognitive domains, including verbal learning and memory, visual learning and memory, working memory, processing speed, and selective attention; olanzapine improved processing speed and selective attention; and aripiprazole improved visual learning and memory, and working memory. However, the three atypical antipsychotic drugs failed to reveal any significant differences in the composite cognitive scores at the study endpoint. In addition, the three drugs all significantly improved clinical measures without significant differences between the drugs after 6 months. These results suggest that the atypical antipsychotics, olanzapine, risperidone and aripiprazole may improve specific cognitive domains with similar global clinical efficacy. In clinical practice, it may be feasible to choose corresponding atypical antipsychotics according to impaired cognitive domains.

Risperidone as a treatment for childhood habitual behavior.

Objective:The aim of this study was to investigate the effect of adding risperidone to the general behavioral treatment of masturbation in children 3-7 years old.Methods:A 4 week randomized clinical controlled trial was designed in year 2009. Samples have been chosen from children who have been referred to the Child and Adolescence Psychiatric Clinic of Isfahan University of Medical Sciences. Ninety children were recruited at the study and randomly allocated into the risperidone and control groups (44 and 46 respectively). The risperidone group was medicated simultaneously by behavioral treatments and 0.25-1 mg of risperidone daily while the controls only received the behavioral treatments.Findings:The mean ± SD age of the risperidone and control groups was 5.3 ± 1.1 and 4.9 ± 1.1 years, respectively. The mean ± SD of the period of suffering from masturbation was 3.4 ± 1.2 and 3.8 ± 1.7 months in the risperidone and the control groups, respectively. At the beginning of the study, the mean frequency of masturbation in control and the risperidone groups was 2.6 ± 0.9 and 2.7 ± 0.9 times/day, whereas after the 4th week, it decreased to 1.4 ± 0.6 and 1.1 ± 0.5 times/day, respectively. The results showed a more reduction in the mean frequency of masturbation in the risperidone group significantly.Conclusion:In comparison to the general behavioral treatment, risperidone in addition to the behavioral treatment will probably reduce the frequency of masturbation in children more effectively.

1956 – Comparison of serum prolactine levels between risperidone and paliperidone extended-release in female patients with schizophrenia

Introduction Paliperidone extended-release (ER) is an atypical antipsychotic that presents the active metabolite of risperidone (9-hydroxyrisperidone) using OROS® technology [1]. Multinational placebo-controlled studies have shown paliperidone ER 3- 15 mg/day to be both efficacious and safe, with discontinuation rates due to adverse events (AEs) similar to placebo [2]. Methods Seventy-eight female patients who were diagnosed as schizophrenia according to DSM-IV-TR and who were started on the treatments of risperidone or paliperidone included to present study. The serum prolactine levels were measured before and after 5 weeks of treatment. Results The 35 of patients were treated with paliperidone, while 43 patients were given oral risperidone treatment. The increases in serum prolactine levels were significant in both groups (p≤0.001), however the increase was much more in paliperidone group. Furthermore, discontinuation rates due to indirect effects of prolactine increase such as galactorrhea, amenorrhea were higher in paliperidone group compared with risperidone group. Discussion Beside the efficacy and well tolerability of paliperidone extended-release, the increase of prolactine level and associated side effects should be carefully assessed during treatment specifically in young women patients.

Follow-Up Study of a Pharmacovigilance Signal

Pharmacovigilance studies of spontaneous adverse event report databases are used to raise hypotheses about potential safety events. Such studies have found a disproportionately higher number of pituitary tumor reports for risperidone. Because there is a high prevalence of clinically "silent" pituitary adenomas, any increased workup in risperidone users, for example, secondary to hyperprolactinemia, might account for the increased reports. We undertook a detailed study of medical record-confirmed newly diagnosed pituitary tumors with mass effect in patients prescribed antipsychotics to evaluate the effect of risperidone. We conducted retrospective studies in 2 large administrative health care databases with access to medical records. Patients were classified into risperidone or other atypical antipsychotic exposure groups. Records with administrative codes indicative of possible cases in the follow-up period were reviewed to confirm the diagnosis of new pituitary tumor and presence of mass effects. The hazard ratio of confirmed pituitary tumors with mass effect was 1.0 (95% confidence interval, 0.5-1.9). Whereas the precision of the hazard ratio was limited by low event rates, despite examination of 409,823 patients' records, ancillary analyses supported the interpretation of no elevated risk. Evidence was found for detection bias that may explain previous pharmacovigilance findings. There was no evidence of increased risk of pituitary tumor with mass effect with risperidone in either cohort or case-control analyses. We cannot rule out a small risk (<2-fold), or a risk that may develop with additional years of exposure or follow-up, or a risk of microadenomas or prolactinomas.

Risk of Hyperprolactinemia and Sexual Side Effects in Males 10–20 Years Old Diagnosed with Autism Spectrum Disorders or Disruptive Behavior Disorder and Treated with Risperidone

The aim of this study was to investigate the long-term treatment effects of risperidone on prolactin levels and prolactin-related side effects in pubertal boys with autism spectrum disorders (ASD) and disruptive behavior disorders (DBD). Physical healthy 10-20-year-old males with ASD (n=89) and/ or DBD (n=9) chronically treated (mean 52 months, range 16-126 months) with risperidone (group 1, n=51) or not treated with any antipsychotic (group 2, n=47) were recruited to this observational study from the child psychiatry outpatient clinic. Morning non-fasting serum prolactin levels were measured and prolactin-related side effects were assessed by means of questionnaires and physical examination. Group differences were tested with Student's t, χ(2), Fisher exact, and Mann-Whitney tests, and logistic regression analysis, according to the type and distribution of data. Hyperprolactinemia was present in 47% of subjects in group 1 but only in 2% of subjects in group 2 (odds ratio 71.9; 95% CI, 7.7; 676.3). Forty-six percent of subjects in group 1 had asymptomatic hyperprolactinemia. Current risperidone dose and 9-OH risperidone plasma level were significant predictors of hyperprolactinemia (p=0.035 and p=0.03, respectively). Gynecomastia and sexual dysfunction were present in 43% and 14% of the subjects in group 1, respectively, compared with 21% and 0% of subjects in group 2 (p=0.05 and p=0.01). Gynecomastia was not significantly associated with hyperprolactinemia. Hyperprolactinemia is a common side effect in young males treated over the long term with risperidone. Young males treated with risperidone are more likely to report diminished sexual functioning than are those not treated with antipsychotics.

Atypical Antipsychotic Use and Parkinsonism in Dementia: Effects of Drug, Dose, and Sex

BackgroundDifferences between atypical antipsychotics in their potential to cause parkinsonism and risk factors for antipsychotic-induced parkinsonism are not well established. There is a particular paucity of information on this in real-world use of these drugs, outside of clinical trial settings. ObjectiveWe compared the incidence of parkinsonism after new treatment with risperidone, olanzapine, or quetiapine in patients with dementia and examined the effects of dose and sex on the risk of parkinsonism. MethodsAdministrative data from Ontario, Canada between 2002 and 2010 were used to compare the incidence of a diagnostic code for parkinsonism or prescription of an anti-Parkinson medication among patients with dementia who were newly prescribed quetiapine, olanzapine, or risperidone. ResultsFrom 15,939 person-years of observation, 421 patients developed parkinsonism. Using low-dose risperidone as the reference group, the adjusted hazard ratios for developing parkinsonism were 0.49 (95% CI, 0.07–3.53) for low-dose olanzapine and 1.18 (95% CI, 0.84–1.66) for low-dose quetiapine. Comparing across drugs within the most commonly prescribed dose ranges, the incidence of parkinsonism was higher in the medium-dose olanzapine group compared with the low-dose risperidone group (hazard ratio 1.66; 95% CI 23–2.23). The adjusted hazard ratio for developing parkinsonism for men (compared with women) was 2.29 (95% CI, 1.88– 2.79). ConclusionsWe found no evidence that the risk of drug-induced parkinsonism in older adults with dementia was different among quetiapine, olanzapine, or risperidone, challenging the notion that the drugs differed in their propensity to cause parkinsonism. Men appeared to be at higher risk of parkinsonism as a adverse event than women.

Long-Term Effect of Haloperidol, Olanzapine, and Risperidone on Plasma Prolactin Levels in Patients With First-Episode Psychosis

The main goal of this study was to assess the long-term effect of haloperidol, olanzapine, and risperidone on serum prolactin levels in a naturalistically treated first-episode psychosis population. Patients included in this study were drawn from a prospective, randomized, open-label clinical trial. Prolactin levels were measured in 110 patients with medication-naive first-episode psychosis at baseline, 3 months, and 1 year. A repeated-measures analysis of variance revealed a significant difference between treatments (F = 17.28, P < 0.001). At 1-year follow-up, most patients in the haloperidol and olanzapine arms had prolactin values that fell within the reference range. Patients treated with risperidone experienced a significant increase at 3 months resulting in prolactin levels above the reference range in 90% of men and 87% of women. The levels showed a tendency to decrease at 1 year, although still more than 70% of the values remained above the normative range. Sexual adverse drug reactions at 1 year assessed by the Udvalg for Kliniske Undersogelser scale showed that a higher percentage (39.3%) of patients had symptoms in the risperidone group compared to the olanzapine group (24%) or haloperidol group (20%), but the difference did not reach statistical significance (P = 0.281). Olanzapine and haloperidol treatments do not significantly affect serum prolactin levels at long term. After 1 year, elevated prolactin levels persist in most patients treated with risperidone.

Use of Risperidone in Cardiac Surgery Patients with Subsyndromal Delirium

We read with great interest the recent study by Hakim et al. , which presented data suggesting that the use of risperidone in cardiac surgery patients with symptoms of subsyndromal delirium may prevent the progression to delirium.1We believe additional information is necessary to interpret the clinical significance of their observations.Screenings for subsyndromal delirium occurred every 8 h in the intensive care unit, with the initial screening 4 h after extubation. The timing of development of subsyndromal delirium is important, as symptoms developing shortly after extubation may be because of residual anesthetics (particularly benzodiazepines and narcotics used in the operating room), and treatment with antipsychotic agents at this point may not have been prudent. Indeed, this point is particularly important with the observation that neither intensive care unit length of stay, nor the duration of clinical delirium, was significantly shortened in the risperidone group. It would also be helpful to know if the intensive care unit and ward in which the study was conducted already practiced risk-factor management techniques shown to decrease delirium incidence in hospitalized elderly patients.2Although prevention of postoperative delirium may be important, it is also important to distinguish between symptoms directly related to residual anesthetics that would improve on their own, and those that require antipsychotic therapy.*Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. j.raiten@gmail.com

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Comparison of quetiapine and risperidone in Chinese Han patients with schizophrenia: results of a single-blind, randomized study

Objective:To evaluate the efficacy and safety of 750 mg/day quetiapine fumarate (Seroquel) in the treatment of Chinese Han patients with schizophrenia.Methods:In this 6-week, multicenter, randomized, rater single-blind study, a total of 119 patients with schizophrenia were randomly assigned to quetiapine (n = 60, 750 mg/day) or risperidone (n = 59, 4 mg/day). The efficacy was assessed by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression–Change (CGI-C) and the Calgary Depression Scale for Schizophrenia (CDSS). Safety and tolerability assessments included treatment-emergent adverse events, laboratory tests and electrocardiograms.Results:The primary analysis demonstrated no significant difference between treatment in the two groups (quetiapine vs. risperidone: 31.9 ± 17.5 vs. 33.3 ± 17.3; P = 0.668). Improvements with both treatments were comparable for total PANSS, positive and negative subscores, general psychopathology subscales, and excitement and attack symptoms. Improvements in CGI-S were similar between treatment groups (P = 0.046). A more favorable trend was detected for quetiapine than risperidone in the reduction of CDSS scores from baseline, especially at week 1 (1.1 ± 2.2 vs. 0.3 ± 2.1, P < 0.050).The rate of extrapyramidal symptom (EPS) and hyperprolactinemia-related adverse events was significantly lower in the quetiapine group than the risperidone group (13.3% vs. 43.3%, P < 0.001). Dizziness and somnolence were more common in the quetiapine group than the risperidone group.Conclusion:Quetiapine fumarate (750 mg/day) has broad clinical efficacy comparable to 4 mg/day risperidone. Dizziness was common in the quetiapine group (P = 0.029), but the rate of somnolence was similar between the two groups (P = 0.114). EPS and hyperprolactinemia rates were significantly higher with risperidone (P < 0.001). Key limitations of this study include small sample size, short treatment periods, and no increase to 6 mg/day for risperidone because of its safety profile.

Effects of ziprasidone and risperidone on cognitive inhibition function through visual pathway of patients with paranoid schizophrenia

Objective To explore the effects of ziprasidone and risperidone on cognitive inhibition function through visual pathway of patients with paranoid schizophrenia. Methods In the open-label, flexible-dosage trial, 124 patients with paranoid schizophrenia were randomly divided into ziprasidone group(120-160 mg/d)and risperidone group(4-8 mg/d) for treatment of 8 weeks. They were assessed with computerized Color Word Test(CWT) and Continuous Performance Test(CPT) through visual pathway for cognitive inhibition function, Positive and Negative Syndrome Scale for efficacy on baseline and 8th weekend. Results After treatment with ziprasidone, the error number (3.12±5.23), the time per correct answer((1.92±1.38)s) of CWT, as well as the double-digit mistaken number (2.31±3.76)and the three-figure mistaken number(3.15±2.80) of CPT reduced more than those before medication ((4.60±6.80), ( 2.74±1.52 )s, (3.85±3.62), (4.42±3.53)) (P<0.05). In risperidone group, the double-digit mistake number of CPT(3.39±3.59) after pharmacotherapy reduced more than that before pharmacotherapy(4.23±3.88) (P<0.05). After treatment the time per correct answer of CWT and the mistaken numbers of CPT in ziprasidone group were less than those in risperidone group(P<0.05), meanwhile, the scores of PANSS in two groups were significantly lower than those before treatment (P<0.01). Conclusion It is effective for ziprasidone and risperidone to improve the function of cognitive inhibition on patients with paranoid schizophrenia, but there is more dramatic for ziprasidone in short-term treatment. Key words: Ziprasidone; Risperidone; Paranoid schizophrenia; Cognitive inhibition

Nephrotoxic Effects of Chronically Administered Olanzapine and Risperidone in Male Rats

Objective: Olanzapine and risperidone are members of the atypical antipsychotic family. Even though they are widely used for the treatment of a broad range of symptoms and disorders in psychiatric practice, their effects on kidney are little known. Nevertheless, the toxic features of these medicines on the tissues, organs or systems other than the kidneys have been demonstrated previously. For these reasons, we aimed to evaluate the effects of long-term administration of low- and high-doses of olanzapine and risperidone on rat kidneys in the present study. Methods: Twenty five rats were divided into 5 groups equally: a control group (CG), a low-dose olanzapine group (LOG), a high-dose olanzapine group (HOG), a low-dose risperidone group (LRG), and a high-dose risperidone group (HRG). Olanzapine in doses of 0.5 and 2.5 mg/kg daily for 6 weeks were intraperitoneally injected into the LOG and HOG, respectively. Similarly, risperidone in doses of 0.5 and 1 mg/kg daily for 6 weeks were intraperitoneally injected into the LRG and HRG, respectively. Same volume and dosages of normal saline (0.9% NaCl) were given to the CG during the same period. At the end of the experiment, the kidneys were dissected out and evaluated histopathologically. Results: Although there were any abnormalities in the LOG, it was determined significant nephrotoxic effects, including losing regularities in both tubular and glomerular structure of kidneys, focal necrosis in some area of renal cortex and medulla, cells with pyknotic nuclei and eosinophilic cytoplasm in both glomerular capillaries and mesangium, an increase in thickness of basal membrane of intraglomerular capillary, especially in parietal layer of Bowman’s capsule, and in some fields, abnormalities caused by the loss of tubule cells, such as hydropic vacuolization and eosinophilic accumulations in the HOG, LRG, and HRG. Conclusion: Albeit it has been hypothesized that these nephrotoxic effects are due to the oxidative stress and mitochondrial dysfunction associated antipsychotic treatment, the definite mechanisms of the nephrotoxicity continue uncertain. On the other hand, nephrotoxicity that presents with cells and casts in the urine, oliguria, proteinuria, elevated serum creatinine, and elevated urea may occur easily in some individuals and these agents should be used cautiously, particularly in patients with renal disease. Because some toxicity here is dose-dependent, there might be an advantage of preferring minimum therapeutic doses with chronic administration to decrease their side effects on the kidney in these special conditions. However, further research is surely needed to study the causal relationship between atypical antipsychotic use and nephrotoxicity.

Different safety profiles of risperidone and paliperidone extended‐release: a double‐blind, placebo‐controlled trial with healthy volunteers

The present study investigated subjective experiences related to secondary negative symptoms and cognitive performance in healthy volunteers in response to the repeated administration of paliperidone extended-release (ER) and risperidone in a double-blind, placebo-controlled trial. Participants (n = 32) received a fixed dose of one of three study medications for three consecutive days: 6 mg of paliperidone ER, 3 mg of risperidone, or placebo. Subjects were evaluated at baseline and after the first and third administrations of the medications by using the Neuroleptic-Induced Deficit Syndrome Scale and the Scale for the Assessment of Negative Symptoms. Cognitive function was measured at baseline and after the third administration of the medications by using the computerized neuropsychological test. Risperidone was associated with more detrimental subjective experiences compared with paliperidone ER and placebo (p < .05), and these differences persisted after controlling for mental and physical sedation. Analysis of computerized neuropsychological test variables revealed significant differences in the changes in Stroop word-color test results from baseline between the paliperidone ER and risperidone groups (p < .005) and between the placebo and risperidone groups (p < .005). These results suggest that paliperidone ER may have a better safety profile than risperidone in terms of negative subjective experiences and cognitive function among normal volunteers.