Lurasidone in Schizophrenia Management: A Comprehensive 12-Week Post-Marketing Surveillance Study in Chinese Patients

Risperidone is a newly available atypical antipsychotic agent that has been reported to be associated with fewer extrapyramidal side effects (EPS) than conventional neuroleptics in adults with schizophrenia. This study assessed the safety and efficacy of risperidone in 16 children and adolescents (aged 9-20 years, mean 14.9 years) who were clinically diagnosed with psychotic disorders: 13 patients met DSM-III-R criteria for schizophrenia, 2 met criteria for schizoaffective disorder, and 1 had schizophreniform disorder. Eleven of the 16 patients had previous unsuccessful neuroleptic trials. Patient charts were reviewed by the patients' child and adolescent psychiatrist for diagnoses, clinical changes, and adverse events. Clinical response was assessed retrospectively using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) scale. With the risperidone dose titrated gradually, an optimal clinical response was found at a mean daily risperidone dose of 5.93 mg (range 2-10 mg). All but one of the 16 patients had an adequate clinical response to risperidone therapy. Statistically significant improvements were found in the CGI (p < 0.0001), the BPRS Total Score (p < 0.0001), and the BPRS Negative Symptom Score (p < 0.001). In general, only mild drug-induced side effects were experienced, with 5 patients developing mild sedation and 3 developing EPS. Risperidone appeared to be safe and effective in ameliorating symptoms of schizophrenia in this age group. It is speculated that the gradual titration of risperidone was crucial in achieving a relatively low rate of EPS.

The efficacy and safety of switching to olanzapine were investigated in patients with first-episode schizophrenia who failed to attain an adequate clinical response to an initial therapeutic trial of risperidone (2-6 mg/day for 12 weeks). A total of 58 first-episode patients with DSM-IV schizophrenia who had residual symptoms following treatment with risperidone were enrolled in an open-label, 12-week study of olanzapine. Dosing was determined by clinical judgment. The main efficacy measure was the Brief Psychiatric Rating Scale (BPRS). Patients with a 20% or greater decrease in BPRS total score plus a final Clinical Global Impressions-Severity of Illness scale score of <or= 3 (mildly ill) were considered responders. The study was conducted from April 2001 to March 2005. Fifty-one patients completed the study, and 7 discontinued due to side effects and medication noncompliance. The mean dosage of olanzapine was 15.3 (SD 4.2) mg/day at study endpoint. Total BPRS scores significantly decreased (12.3%) during olanzapine treatment (p < .001). In addition, BPRS subscales of anxiety/depression and excitement significantly decreased (19.1% and 29.5%, respectively; p < .001). The responder rate was 29.3% (17/58). BPRS positive symptom subscale score at baseline was significantly higher in nonresponders compared to responders (p < .001). Comparison of percentage change in BPRS total scores between responders and nonresponders revealed a significant difference at week 4 that continued until study endpoint (p < .001). Of 58 patients, 27 (46.6%) showed clinically significant weight gain (>or= 7%) from baseline. Although we cannot draw any conclusion from a study without a control group, favorable outcomes and good tolerance were observed after switching to olanzapine from risperidone in our population. In addition, factors that predicted a good overall response included a relative absence of positive symptoms at baseline and the percentage reduction in total BPRS score at 4 weeks of treatment. Double-blind, crossover trials are needed to confirm these observations.

This study was conducted to determine whether the addition of naltrexone to ongoing neuroleptic treatment would facilitate the reduction in positive or negative symptoms in patients with schizophrenia. Twenty-one patients meeting DSM-III criteria for schizophrenia were enrolled; all patients had been stabilized for at least 2 weeks on their dosage of neuroleptic medicine before entering the study. Patients were randomized to receive either placebo or naltrexone 200 mg/day for 3 weeks in addition to their neuroleptic. Patients randomized initially into the placebo arm were crossed over to receive naltrexone in a single-blind fashion for 3 additional weeks. All patients were rated weekly with the Brief Psychiatric Rating Scale (BPRS). Fifteen patients received placebo and six received naltrexone in the first 3 weeks. No significant effects of naltrexone on total BPRS scores or BPRS subscale scores were observed. Patients who received naltrexone on a single-blind basis at the end of the placebo-controlled trial demonstrated a transient exacerbation in negative symptoms as reflected by the total BPRS score and the BPRS Withdrawal-Retardation subscale score. Repeated-measures analysis of variance (ANOVA) on the BPRS total score of the subsequent treatment with naltrexone showed a trend for a significance in the drug by time effect. Repeated-measures ANOVA on the BPRS Withdrawal-Retardation subscale of the subsequent treatment with naltrexone showed a significant drug by time effect. The current data failed to indicate a clinical benefit when naltrexone was added to the neuroleptic regimen. Other potential applications of naltrexone in schizophrenia are addressed.

\nBackground: Accumulating evidence suggests minocycline (MINO) is effective as an adjunct treatment in schizophrenia. We previously reported significant improvement in avolition, anxiety/depression and working memory and a trend for positive symptoms and total Brief Psychiatric Rating Scale (BPRS) scores with MINO in a double-blind, placebo-controlled trial. We also found a &gt;30% reduction in total BPRS scores in 25% of the MINO group compared to 4% in placebo (PÂ =Â .04). Here we examine variables associated with symptom improvements.

We compared the response with electroconvulsive therapy (ECT) of bipolar I patients resistant to pharmacological treatment, who presented depression or mixed state (MS). Ninety-six bipolar I patients according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition were included in the study (46 with major depressive episode and 50 with MS). Bilateral ECT was delivered using a brief pulse stimulator Mecta 5000Q (Mecta Corp, Lake Oswego, Ore) on a twice-a-week schedule. The patients were evaluated before ECT (baseline) and a week after the ECT course (final score), using the Hamilton Rating Scale for Depression (HAM-D), Mania Rating Scale, Brief Psychiatric Rating Scale (BPRS), and Clinical Global Improvement (CGI). Global response rate (CGI <or=2) was similar in bipolar depression and MS (67.4% and 76.0%, respectively); no difference was found in global remission rate (CGI <or=1) between depression (41.3%) and MS (34.8%). The response rate of depressive symptoms (HAM-D <or=50% was 69.6% for bipolar depression and 66.0% for MS; remission rate (HAM-D <or=8) was 26.1% and 30.0%, respectively. At the end of the ECT course, CGI-Severity, HAM-D total, Young Mania total, BPRS total, and psychotic cluster scores showed a progressive reduction in both groups. A significant group effect was present for Young mania total score, BPRS total score, and psychotic cluster. With the exception of anticonvulsants, concomitant psychotropic medications were permitted during ECT course, based on the physician's decision. Electroconvulsive therapy should be considered a viable treatment alternative in bipolar I patients with depression or MS who do not respond to conventional pharmacologic management. The only difference is that MS may present more residual agitation or psychotic features in comparison with depressive patients.

Melperone in the treatment of neuroleptic-resistant schizophrenia

The difference of social cognitive and neurocognitive performance between patients with schizophrenia at different stages and influencing factors

Objective To explore the efficacy of periodical rehabilitation directive nursing in schizophrenic patients during recovery. Methods 80 outpatients of schizophrenia during recovery were randomly divided into two groups. All the subjects were treated with effective anti-psychotics. The study group ( n = 40) were treated with periodical rehabilitation directive nursing once a month for half a year; the control group ( n =40) were given with general health educations. The two groups were tested with the Brief Psychiatric Rating Scale (BPRS) and Social Disability Screening Schedule (SDSS) before intervention and after half a year of intervention. The data of two groups were compared. Results Compared with control group, the total scores of BPRS and SDSS, and the factors' scores of occupational functions, social activity, family duty and life ability in the study group were significantly decreased (P ＜ 0. 05 ). The treatment dependence and social activity participation in study group were superior to those in the control group ( P ＜ 0. 05), while the accident event incidence was lower(P ＜0. 05). The ratio of re-work in the study group was higher but the re-onset rate in half a year was lower than that of the control group ( P ＜ 0. 05 ). Conclusions Periodical rehabilitation directive nursing in schizophrenic patients during recovery has showed better efficacy. It was important in controlling illcondition, improving treatment dependence and social function, decreasing incidence of accident event. Key words: Schizophrenia; Health education; Rehabilitation; Periodical rehabilitation directive nursing

Objective: The efficacy and safety of adjunctive magnetic seizure therapy (MST) for patients with schizophrenia are unclear. This systematic review was conducted to examine the efficacy and safety of adjunctive MST for schizophrenia.Methods: Chinese (WanFang and Chinese Journal Net) and English (PubMed, EMBASE, PsycINFO, and the Cochrane Library) databases were systematically searched.Results: Two open-label self-controlled studies (n = 16) were included and analyzed in this review. In these studies, the Positive and Negative Syndrome Scale (PANSS) total scores and Brief Psychiatric Rating Scale (BPRS) total scores significantly decreased from baseline to post-MST (all Ps < 0.05), without serious adverse neurocognitive effects. Mixed findings on the neurocognitive effects of adjunctive MST for schizophrenia were reported in the two studies. A discontinuation rate of treatment of up to 50% (4/8) was reported in both studies. The rate of adverse drug reactions (ADRs) was evaluated in only one study, where the most common ADRs were found to be dizziness (25%, 2/8) and subjective memory loss (12.5%, 1/8).Conclusion: There is inconsistent evidence for MST-related adverse neurocognitive effects and preliminary evidence for the alleviation of psychotic symptoms in schizophrenia.

Prior early prediction models for antipsychotic treatment response demonstrate good specificity but poor sensitivity (i.e., high false-negative rates). The purpose of this study was to refine the early prediction model in schizophrenia patients taking an atypical antipsychotic agent, zotepine. 135 acutely ill inpatients with DSM-IV-defined schizophrenia received 4 weeks of 150 mg/day zotepine treatment. Psychopathology severity was assessed weekly with the Brief Psychiatric Rating Scale (BPRS) and subscales for positive, negative, and general symptoms. Clinical response was defined as a reduction of 20% or more in the BPRS total score at week 4. A logistic regression model was used to obtain early predictors. The receiver operating characteristic curve was employed to determine the optimal cutoff points of the variables for predicting response. The study was conducted from June 2004 to April 2005. The most significant early predictors for ultimate response at week 4 were BPRS positive subscale score changes at week 1 and, better, at week 2 (p < .001 at both timepoints). At week 1, a BPRS positive score reduction of 4 appeared to be the optimal cutoff point for predicting eventual response, providing a sensitivity of 0.77 and specificity of 0.77. At week 2, a BPRS positive score reduction of 6 was the best for prediction, with a sensitivity of 0.83 and specificity of 0.91. These findings suggest that using the first 2 weeks' improvement in positive symptoms to predict the fourth week's treatment response is favorable in terms of both specificity and sensitivity. Further studies are needed. Moreover, whether this model could be applied to establish a prediction system for other antipsychotics or other psychotropics also deserves research.

Relationship between self-reported and clinician-rated psychopathology in youth psychiatric outpatients

To find biomarkers to assess the risk of aggression, we looked at the association between aggression and levels of body inflammation in patients with schizophrenia. The Modified Overt Aggression Scale (MOAS) score was used to divide the aggressive (n = 72) and nonaggressive (n = 141) groups. The Brief Psychiatric Rating Scale (BPRS) is a tool for determining the severity of a patient's condition. After measuring the number of inflammatory cells in the peripheral blood, the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and monocyte-lymphocyte ratio (MLR) were estimated. We investigated the relationship between aggressive behavior, bodily inflammation, and BPRS. Before therapy, the aggressive group's BPRS score, white blood cell (WBC) count, neutrophil count, monocyte count, NLR, and MLR were considerably more significant than the nonaggressive group's. After therapy, statistically significant variations in total BPRS score and neutrophil count between the two groups. According to correlation analysis before and after treatment, aggressive behavior was positively connected with neutrophil count, NLR, and BPRS score. The presence of aggressive behavior in schizophrenic patients indicates the severity of the disorder to some degree. NLR can be used as an objective biomarker to quickly assess the risk of aggression in schizophrenic patients.

Prolactin response to d-fenfluramine challenge test as a predictor of treatment response to haloperidol in acute schizophrenia

Back to table of contents Previous article Next article Letter to the EditorFull AccessLetters to the EditorCorrado Barbui, M.D., Corrado BarbuiSearch for more papers by this author, M.D., Milan, ItalyPublished Online:1 Jan 1998https://doi.org/10.1176/ajp.155.1.152aAboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail TO THE EDITOR: Tollefson and colleagues presented the results of a multicenter, double-blind, collaborative trial that reported a superior and broader spectrum of efficacy in the treatment of schizophrenia, with a substantially more favorable safety profile, for olanzapine than for haloperidol. It is worth noting, however, that there are at least four aspects in this trial that need further attention.It was surprising that despite the international and collaborative nature of the study, the 174 sites that took part were not cited in the article. They were from Europe and North America and recruited both in- and outpatients, but further details were not given. Information on the characteristics of these centers would have been of value in interpreting the data presented, since there was great variability in the number of patients who entered the trial at each center (from one patient in 13 sites to 73 patients at one center). Differences among the centers (e.g., urban versus rural, in- versus outpatient services) might have been a valid reason for such variability, but different enrollment criteria might also have been responsible. This possibility is further supported by the fact that a quite heterogeneous population was recruited. While the majority of the patients had schizophrenia of the paranoid subtype, no information is provided on the number of schizophrenic patients included or their distribution between the two treatment arms, nor is there information on the distribution of chronic patients. In addition, it would have been of interest to know the proportion who were enrolled during an exacerbation of their illness. Around 77% of the group were intolerant of current antipsychotic therapy (excluding haloperidol), but no details on how this intolerance was measured are provided. Finally, patients were required to have a minimum Brief Psychiatric Rating Scale (BPRS) score of 18, but no reason is provided to justify this choice. Overall, it is not clear to which patients the results of the present trial apply.The study compared olanzapine, 5–20 mg/day, to haloperidol, 5–20 mg/day. The baseline severity of illness scores showed that the haloperidol-treated patients had significantly higher mean total scores on the BPRS and the Positive and Negative Syndrome Scale. In other words, the comparison group had more severe symptoms than the experimental group at baseline. In addition, the haloperidol group received lower drug doses than the olanzapine group during the acute phase of the study. Hence, one cannot rule out the possibility that this unbalanced situation may have hampered the results of the trial, in terms of both efficacy and safety.The study supported the notion that olanzapine had significant advantages over haloperidol in terms of negative symptoms and extrapyramidal side effects. However, it would have been useful to consider the temporal relationship between negative symptoms and extrapyramidal side effects in order to rule out the possibility of an association. In fact, an improvement in negative symptoms may be due to resolution of “secondary,” i.e., extrapyramidal, symptoms, as has been proposed for clozapine (1). If this association holds, any advantage of a new neuroleptic in terms of extrapyramidal and negative symptoms should not be tested against haloperidol, since this drug produces more extrapyramidal side effects than other typical neuroleptics and therefore cannot be considered the “gold standard.”Finally, it would have been helpful to have details on the blind nature of the trial. No information is provided on efforts to ensure blind data analysis, or “triple masking” (2), a procedure that is now becoming common.

OCCURRENCE OF RISK FACTORS FOR SCHIZOPHRENIA AMONG OLD AND YOUNG FATHERS