Mean Positive And Negative Syndrome Scale Total Scores Research Articles

Relationship between plasma risperidone concentrations and clinical features in chronic schizophrenic patients in China.

Prior studies have noted great variability in the plasma levels of risperidone (RIS). Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption, metabolism, and other predictors of metabolic dysregulation; however, these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain. To ascertain the characteristics of chronic schizophrenic patients treated with RIS, and to assess their relationship with plasma RIS levels. This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service. The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography. The patients' demographic and clinical characteristics, and psychopathologies were assessed, and the associations between clinical variables and plasma levels of RIS were explored. Male patients received higher doses of RIS than female ones, but plasma concentrations of RIS and risperidone + 9-hydroxyrisperidone (active moiety) were higher in female patients. Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale (PANSS) were significantly positively correlated with plasma concentrations of risperidone + 9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects. In male subjects, we found a statistically significant positive correlation between the concentrations of risperidone + 9-hydroxyrisperidone in plasma/(dose × kg) and age, mean PANSS negative subscale scores, mean PANSS general psychopathology subscale scores, and mean PANSS total scores. Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.

Laterality of cognitive dysfunction in schizophrenia: A cross-sectional study

Background: Clear localization (or) related deficits would make gateways for forming rehabilitation strategies much needed to enhance functionality in schizophrenia. We aimed to study the neuropsychological dysfunction including laterality in schizophrenia patients by using the native All India Institute of Medical Sciences Comprehensive Neuropsychological Battery (AIIMS CNB) in Hindi Adult form. Materials and Methods: In a cross-sectional study design, 40 right-handed schizophrenia patients in the age range of 18–59 years with primary education who can read and write were purposively recruited. Neuropsychological assessment and psychopathology were assessed by AIIMS CNB and Positive and Negative Syndrome Scale (PANSS), respectively. Raw scores and T-scores were recorded, and lateralization scores were calculated. The localization was estimated by commuting eight lobe scales. Statistical analyses of the quantitative scores were done using IBM SPSS 28. Results: The mean PANSS total scores and dose of chlorpromazine equivalents of the sample were 88.900 ± 9.940 and 497.500 ± 100.607 mg. 62.5% of the participants reportedly had the presence of brain dysfunction based on T-scores. Right hemispheric lateralization of cognitive deficits was present markedly in 95% of schizophrenia subjects. As per lobe scale scores, the right sensory-motor lobe (60%) and the right frontal lobe (27.5%) were found to be most dysfunctional. Conclusion: Majority of schizophrenia patients are dysfunctional as per AIIMS CNB and have hemispheric lateralization (right) of deficits. Our findings challenge the loss of asymmetry verdicts in schizophrenia.

Asian Subgroup Analysis of the REMISSIO Study: A Long-Term Efficacy and Safety Study of Paliperidone Palmitate 3-month Formulation in Patients with Stable Schizophrenia in a Naturalistic Clinical Setting.

ObjectiveTo evaluate the long-term efficacy and safety of three-monthly paliperidone palmitate (PP3M) in Asian patients with stable schizophrenia in a naturalistic setting.MethodsAsian patients recruited between May 2016 and March 2018 from the prospective, single-arm, non-randomized, open-label, multi-national REMISSIO study were analyzed. Patients received PP3M over 12 months following ≥ 4 months of treatment with one-monthly paliperidone palmitate. The primary efficacy endpoint was the proportion of patients who achieved symptomatic remission. Other endpoints were changes in Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) total scores, hospitalization rates, and safety.ResultsA total of 71 patients (23.3%) were Asian (South Korea 33, Malaysia 21, Taiwan 17); 95.8% of patients completed the study. At LOCF, 71% of Asian patients achieved symptomatic remission compared to the overall population (n = 172/303, 56.8%). Improvements in mean (standard deviation) PANSS and PSP total scores from baseline to LOCF in Asian patients and overall population were clinically significant. A lower proportion of Asian patients had ≥ 1 psychiatric hospitalization after PP3M treatment (n = 1/70, 1.4%) than during the 12 months before (n = 12/70, 17.1%); compared with patients in the overall population after (n = 8/303, 2.6%) and before PP3M treatment (n = 37/303, 12.2%). The overall incidence of treatment-emergent adverse events across Asian patients was 62.9% compared to 53.1% in the overall population. Safety findings were consistent with the known safety profile of PP3M.ConclusionOur findings confirm existing evidence on the efficacy and tolerability of PP3M in Asian patients with stable schizophrenia over 12 months of treatment.

Driving fitness in clinically stable outpatients with chronic schizophrenia

IntroductionDriving motorized vehicles is an integral part of individual mobility and a key parameter for employment and social integration. This naturalistic, cross-sectional study investigated the associations between driving fitness, residual symptomatology, olanzapine equivalent, and extrapyramidal symptoms (EPS) in long term stable outpatients with schizophrenia. MethodsBeside sociodemographic data, and driving habits, residual symptoms, and EPS were assessed using the Positive and Negative Syndrome Scale (PANSS), and the Modified Simpson Angus Scale (MSAS). PANSS symptoms were analyzed using the Wallwork/Fortgang five-factor model. MSAS cut-off scores ≥3 were defined as positive for EPS. Driving skills were assessed using the Vienna Test System and an expert evaluation. Results50 patients were included into the study. Mean PANSS total scores indicated mild residual symptomatology and EPS were not present in 48% of study participants. 44% passed the driving fitness assessment and were considered as competent to drive, 20% were judged to be partially competent and 36% to be incompetent to drive. With the exception of disorganization (r = −0·287, p = 0·048) residual symptoms of schizophrenia did not correlate with driving fitness. However, moderate negative correlations were detected between driving fitness and the severity of EPS (r = −0·554, p = 0·000), age (r = −0·413, p = 0·003) as well as olanzapine equivalent doses (r = −0·432, p = 0·002). These results were not corrected for multiple comparison. DiscussionThe present findings indicate that up to two thirds of clinically stable outpatients with chronic schizophrenia may be (partially) competent to drive. Both the presence of EPS as well as the dosage of antipsychotic medication seem to be of particular relevance in this regard.

Neurocognitive and clinical correlates of insight in schizophrenia.

Background:Schizophrenia is a heterogeneous disorder characterized by various symptom dimensions and neurocognitive deficits. Impairment of insight is a core clinical symptom of the disorder. There has been an increasing focus on neurocognition and insight in schizophrenia; although, many studies fail to control for premorbid cognitive status.Materials and Methods:Schizophrenia patients (n = 60) selected for adequate background education were recruited from outpatient services of a tertiary care hospital and community care homes in Southern India. These patients were comprehensively assessed using a neurocognitive battery. Clinical assessments were done using the Positive and Negative Syndrome Scale (PANSS) and Schedule for the Assessment of Insight-expanded version (SAI-E). Partial correlation was performed to examine the relationship of insight with clinical and neurocognitive measures. Statistical significance was set at P = 0.004 (Bonferroni correction for 12 tests of association). Linear regression analysis was performed to examine the predictors of insight.Results:The mean PANSS positive, negative, general psychopathology, and total scores were 14.2 ± 4.9, 17.4 ± 5.0, 34.3 ± 6.8, and 65.8 ± 13.9, respectively. Mean insight score (SAI-E) was 8.5 ± 2.9. In partial correlation done after controlling for IQ, significant negative correlations were observed between insight score and the Wisconsin Card Sorting Test (WCST) total errors (P = 0.001), WCST perseverative errors (P < 0.001). Insight scores had negative correlations with PANSS negative (P < 0.002) and total scores (P < 0.002). WCST perseverative errors were the primary predictor of insight in the regression analysis.Conclusion:Insight has a strong relationship with executive functioning in schizophrenia. This could indicate shared neurobiological substrates for insight and executive functioning.

Effects of paliperidone extended release on hostility among Thai patients with schizophrenia.

ObjectiveThis open-label prospective study investigated the effects of paliperidone extended release (ER) on hostility in Thai patients with schizophrenia.BackgroundPatients diagnosed with schizophrenia may be hostile or exhibit aggressive behavior, which can occasion their admission to psychiatric hospital. Antipsychotic medications are often used to treat hostility and aggression in such patients. Paliperidone ER is effective and well tolerated in the treatment of schizophrenia. However, there are no data available for paliperidone ER with regard to its efficacy on hostility and aggression among Thai patients. This study was a part of the PERFEcT study, a 6-month, open-label, multicenter, multicountry, prospective trial to explore the safety, efficacy, and functionality of paliperidone ER tablets. The current study included only the data obtained from Thai participants.Materials and methodsFlexible dosing of paliperidone ER in a range of 3–12 mg/day was used, allowing investigators to adjust the dosage of each subject individually. The 199 Thai patients had a stable Clinical Global Impression – severity score before enrollment. Demographic data were collected at enrollment, and assessments took place at 1, 2, 3, and 6 months postbaseline. The Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale were used to evaluate efficacy. In this analysis, we report the findings for the specific PANSS factor P7 (hostility) and the PSP subscale disturbing and aggressive behavior. Data were analyzed using paired t-test method to investigate changes in mean PANSS and PSP total and subscale scores. The significance level was set at P<0.05.ResultsFrom a total of 199 Thai patients, 148 patients (74.4%) participated in all visits. There was a significant reduction in mean scores for all total PANSS measures from 1 month onward compared with baseline, as well as ongoing significant reductions in scores from visit to visit. There was a significant reduction in mean hostility score at 2 months (P<0.05), 3 months (P<0.05), and 6 months (P<0.01) (n=148). For the PSP scale, there was a significant across-the-board reduction of mean scores from 3 months onward, including in the disturbing and aggressive behavior subscale (P<0.001) (n=148).ConclusionSwitching from previously unsuccessful antipsychotic treatments to paliperidone ER may be a useful option to reduce hostility and disturbing behavior in patients with schizophrenia. This study in Thai patients is in line with findings in other countries and cultures concerning the management of hostility in patients with schizophrenia.

Paliperidone Palmitate versus Risperidone Long-Acting Injection in Markedly-to-Severely Ill Schizophrenia Subjects

To examine onset of efficacy of two long-acting injectable atypical antipsychotics in markedly-to-severely ill schizophrenia subjects. This subgroup analysis included 292 subjects with baseline Clinical Global Impressions-Severity scores of markedly ill or worse from a 13-week, randomized, double-dummy noninferiority study (NCT00589914). Subjects received either: 1) paliperidone palmitate (PP; 234 mg day 1 and 156 mg day 8 [corresponding to 150 and 100 milligram equivalents of paliperidone, respectively], both administered in deltoid muscle, followed by once-monthly flexible dosing in deltoid or gluteal muscle) and risperidone long-acting injection (RLAI)-matched placebo injections; or, 2) RLAI (25 mg, days 8 and 22; followed by biweekly flexible dosing) and PP-matched placebo injections. RLAI subjects received oral risperidone days 1-28; PP subjects received oral placebo. Because of RLAI's release profile, data through day 22 correspond to oral risperidone. Assessments included Positive and Negative Syndrome Scale (PANSS) and adverse event (AE) reports. Paired t-tests assessed within-group changes. LS mean (SE) PANSS total scores improved significantly (both p<.001) with PP and oral risperidone by day 4 (-5.0 [0.6] and -3.4 [0.6], respectively) through day 22; and with PP and RLAI through end point (-21.5 [1.9] and -18.6 [1.9], respectively). The between-group difference was significant only at day 4 (p=.006). Proportion of subjects with a .30% reduction in PANSS total score was not significantly different between the two groups at day 4 and was significantly greater with paliperidone palmitate than oral risperidone at days 15 and 22 (26.1% versus 12.7%, p=.013; 41.6% versus 32.0%, p=.048, respectively). Most common AEs (.5% in either treatment group): headache (PP 6.3% and RLAI 14.0%), insomnia (10.6% and 10.7%), somnolence (7.8% and 1.3%), akathisia (7.0% and 5.3%), schizophrenia (8.5% and 5.3%), agitation (5.6% and 2.0%), and injection site pain (5.6% and 1.3%). Using the recommended dosing regimens for PP and RLAI, both PP and oral risperidone (used during RLAI initiation) improved symptoms of schizophrenia in markedly-to-severely ill subjects at days 4-22.

Cognitive therapy for people with schizophrenia spectrum disorders not taking antipsychotic drugs: a single-blind randomised controlled trial

Antipsychotic drugs are usually the first line of treatment for schizophrenia; however, many patients refuse or discontinue their pharmacological treatment. We aimed to establish whether cognitive therapy was effective in reducing psychiatric symptoms in people with schizophrenia spectrum disorders who had chosen not to take antipsychotic drugs. We did a single-blind randomised controlled trial at two UK centres between Feb 15, 2010, and May 30, 2013. Participants aged 16-65 years with schizophrenia spectrum disorders, who had chosen not to take antipsychotic drugs for psychosis, were randomly assigned (1:1), by a computerised system with permuted block sizes of four or six, to receive cognitive therapy plus treatment as usual, or treatment as usual alone. Randomisation was stratified by study site. Outcome assessors were masked to group allocation. Our primary outcome was total score on the positive and negative syndrome scale (PANSS), which we assessed at baseline, and at months 3, 6, 9, 12, 15, and 18. Analysis was by intention to treat, with an ANCOVA model adjusted for site, age, sex, and baseline symptoms. This study is registered as an International Standard Randomised Controlled Trial, number 29607432. 74 individuals were randomly assigned to receive either cognitive therapy plus treatment as usual (n=37), or treatment as usual alone (n=37). Mean PANSS total scores were consistently lower in the cognitive therapy group than in the treatment as usual group, with an estimated between-group effect size of -6.52 (95% CI -10.79 to -2.25; p=0.003). We recorded eight serious adverse events: two in patients in the cognitive therapy group (one attempted overdose and one patient presenting risk to others, both after therapy), and six in those in the treatment as usual group (two deaths, both of which were deemed unrelated to trial participation or mental health; three compulsory admissions to hospital for treatment under the mental health act; and one attempted overdose). Cognitive therapy significantly reduced psychiatric symptoms and seems to be a safe and acceptable alternative for people with schizophrenia spectrum disorders who have chosen not to take antipsychotic drugs. Evidence-based treatments should be available to these individuals. A larger, definitive trial is needed. National Institute for Health Research.

EPA-1548 - Flexibly dosed paliperidone palmitate in non-acute patients with schizophrenia switched from previously unsuccessful monotherapy with oral atypical antipsychotics

To explore tolerability, safety and treatment response of flexibly dosed paliperidone palmitate (PP) in adult non-acute schizophrenia patients previously unsuccessfully treated with oral antipsychotic monotherapy of risperidone (RIS), paliperidone ER (Pali ER), olanzapine (OLA), quetiapine (QUE) or aripiprazole (ARI). International, prospective 6-month open-label study. Outcomes were response (≥20% improvement in Positive and Negative Syndrome Scale (PANSS) total score at endpoint), patient functioning (Personal and Social Performance scale (PSP)), treatment-emergent adverse events (TEAEs) and Extrapyramidal Symptom Rating Scale (ESRS). Intent-to-treat population: n=191 (RIS), n=104 (Pali ER), n=87 (OLA), n=46 (ARI), n=44 (QUE). Patients presented some differences in baseline demographics, e.g. in age, years since diagnosis and BMI. Baseline mean PANSS total scores ranged from 74.7±14.9 (ARI) to 70.8±13.1 (QUE) and 70.8±15.1 (RIS). Between 67.4% (ARI) and 83.2% (RIS) of patients completed the study. At endpoint, 74% (RIS), 58% (Pali ER), 61% (OLA), 66% (QUE) and 52% (ARI) of patients had improved ≥20% in PANSS total score. Mean PSP improvement at endpoint was: 10.4±13.8 (RIS), 7.0±13.8 (Pali ER), 4.5±15.9 (OLA), 7.9±12.4 (QUE) and 3.9±13.2 (ARI); all p<0.05. TEAEs reported at least once in all subgroups were injection site pain, insomnia and psychotic disorder. Mean change in ESRS from baseline to endpoint was -1.2±3.5 (RIS), - 0.7±4.1 (Pali ER), -1.3±4.4 (OLA), -0.3±3.2 (QUE) and -0.6±3.4 (ARI; p<0.05 for all except QUE). PP was well tolerated and associated with clinically relevant treatment response in patients previously unsuccessfully treated with oral atypical antipsychotic monotherapy, regardless of the medication that was switched.

Paliperidone palmitate and risperidone long-acting injectable in subjects with schizophrenia recently treated with oral risperidone or other oral antipsychotics.

This post hoc subgroup analysis of a randomized, double-blind trial evaluated the response to treatment with two long-acting injectable atypical antipsychotics, ie, paliperidone palmitate and risperidone long-acting injectable (RLAI), in subjects with schizophrenia experiencing clinically significant symptoms despite recent treatment with oral risperidone only or other oral antipsychotics. Adult subjects were eligible for the 13-week, double-blind, double-dummy trial (NCT00589914) if they had an established diagnosis of schizophrenia for at least one year and a Positive and Negative Syndrome Scale (PANSS) total score of 60-120 inclusive at screening. Subjects received either paliperidone palmitate (234 mg, day 1; 156 mg, day 8; then once-monthly flexible dosing) or RLAI (25-50 mg biweekly, with oral risperidone supplementation on days 1-28), plus matched placebo injections/tablets. This post hoc analysis reports data on 747 subjects who, within 2 weeks of starting double-blind study medication, had reportedly received oral risperidone only (paliperidone palmitate group, n = 126; RLAI group, n = 107), other oral antipsychotics (paliperidone palmitate group, n = 199; RLAI group, n = 203), or no antipsychotic (paliperidone palmitate group, n = 56; RLAI group, n = 56). Mean PANSS total scores improved significantly at end point across all subgroups (mean change from baseline ranged from -17.5 to -19.5, all P < 0.0001). Clinical Global Impression-Severity and Personal and Social Performance scale measures also significantly improved from baseline (all P < 0.0001). Treatment with paliperidone palmitate or RLAI resulted in a significant reduction in the symptoms of schizophrenia irrespective of previous recent treatment with oral risperidone only or other oral antipsychotics. For subjects who had previously received oral risperidone only, the difference in formulation was the main change in the intervention because the molecule delivered remained the same or similar. These data support the contribution of a long-acting formulation to improving the treatment response and suggest that nonadherence may be a significant contributor to inadequate efficacy of oral formulations in subjects with schizophrenia.

Paliperidone Extended Release

Paliperidone, the major active metabolite of risperidone, is an atypical antipsychotic agent formulated as an extended-release (ER) tablet suitable for once-daily oral administration. Paliperidone ER is approved for the treatment of adolescents aged 12-17 years with schizophrenia in the US (the focus of this review). It is also approved for the treatment of adults with schizophrenia or schizoaffective disorder. Paliperidone ER has shown efficacy in the treatment of patients aged 12-17 years with acutely symptomatic schizophrenia in a randomized, double-blind, parallel-group, placebo-controlled, multicenter, 6-week trial. The primary endpoint was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score to day 43 or the final assessment point post-baseline. Patients with a PANSS total score of 60-120 received one of three weight-based, fixed once-daily doses of paliperidone ER (patients weighing 29 kg to <51 kg: 1.5 mg [low-dose], 3 mg [medium], or 6 mg [high]; patients weighing ≥51 kg: 1.5 mg [low], 6 mg [medium], or 12 mg [high]), or placebo. Compared with placebo, significant improvements in mean PANSS total scores were reported for the medium-dose (3-6 mg) paliperidone ER treatment groups. There were no significant differences in mean PANSS total scores between the recipients of low-dose or high-dose paliperidone ER versus placebo. Mean PANSS total scores in the actual dose treatment groups (regardless of weight) decreased from baseline (i.e. improved) and were significantly lower for the 3, 6, and 12 mg groups than for the placebo group. Treatment-emergent adverse events were dose related in adolescents with schizophrenia who received weight-based fixed doses of paliperidone ER.

Lurasidone in the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo- and Olanzapine-Controlled Study

The study was designed to evaluate the short-term efficacy and safety of lurasidone in the treatment of acute schizophrenia. Participants, who were recently admitted inpatients with schizophrenia with an acute exacerbation of psychotic symptoms, were randomly assigned to 6 weeks of double-blind treatment with 40 mg of lurasidone, 120 mg of lurasidone, 15 mg of olanzapine (included to test for assay sensitivity), or placebo, dosed once daily. Efficacy was evaluated using a mixed-model repeated-measures analysis of the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score (as the primary efficacy measure) and Clinical Global Impressions severity (CGI-S) score (as the key secondary efficacy measure). Treatment with both doses of lurasidone or with olanzapine was associated with significantly greater improvement at week 6 on PANSS total score, PANSS positive and negative subscale scores, and CGI-S score compared with placebo. There was no statistically significant difference in mean PANSS total or CGI-S change scores for the lurasidone groups compared with the olanzapine group. With responders defined as those with an improvement of at least 20% on the PANSS, endpoint responder rates were significant compared with placebo for olanzapine only. The incidence of akathisia was higher with 120 mg of lurasidone (22.9%) than with 40 mg of lurasidone (11.8%), olanzapine (7.4%), or placebo (0.9%). The proportion of patients experiencing ≥ 7% weight gain was 5.9% for the lurasidone groups combined, 34.4% for the olanzapine group, and 7.0% for the placebo group. Lurasidone was an effective treatment for patients with acute schizophrenia. Safety assessments indicated a higher frequency of adverse events associated with 120 mg/day of lurasidone compared with 40 mg/day.

Long-acting injectable risperidone in partially adherent and nonadherent patients with schizophrenia

Background:Long-acting injectable antipsychotics may improve medication adherence, thereby improving overall treatment effectiveness. This study aimed to evaluate the effectiveness, safety, and tolerability of risperidone long-acting injection in schizophrenic patients switched from oral antipsychotic medication.Methods:In a 12-month, multicenter, open-label, noncomparative study, symptomatically stable patients on oral antipsychotic medication with poor treatment adherence during the previous 12 months received intramuscular injections of risperidone long-acting injection (25 mg starting dose) every 2 weeks. The primary endpoint was the change in Positive and Negative Syndrome Scale (PANSS) total score.Results:Of the 60 patients who were screened, 53 received at least one injection (safety population), and 51 provided at least one postbaseline assessment. Mean PANSS total scores improved significantly throughout the study and at endpoint. Significant improvements were also observed in Clinical Global Impression of Severity, Personal and Social Performance, and Drug Attitude Inventory scales. Risperidone long-acting injection was safe and well-tolerated. Severity of movement disorders on the Extrapyramidal Symptom Rating Scale was reduced significantly. The most frequently reported adverse events were insomnia (22.6%), increased prolactin (17.0%), and weight gain (13.2%).Conclusion:Risperidone long-acting injection was associated with significant symptomatic improvements in stable patients with schizophrenia following a switch from previous antipsychotic medications.

Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial

BackgroundThis post hoc analysis (trial registration: ClinicalTrials.gov NCT00590577) assessed onset of efficacy and tolerability of acute treatment with once-monthly paliperidone palmitate (PP), a long-acting atypical antipsychotic initiated by day 1 and day 8 injections, in a markedly to severely ill schizophrenia population.MethodsSubjects entering the 13-week, double-blind trial were randomized to PP (39, 156, or 234 mg [25, 100, and 150 mg eq of paliperidone, respectively]) or placebo. This subgroup analysis included those with a baseline Clinical Global Impressions-Severity (CGI-S) score indicating marked to severe illness. PP subjects received a 234-mg day 1 injection (deltoid), followed by their assigned dose on day 8 and monthly thereafter (deltoid or gluteal). Thus, data for PP groups were pooled for days 4 and 8. Measures included Positive and Negative Syndrome Scale (PANSS), CGI-S, Personal and Social Performance (PSP), and adverse events (AEs). Analysis of covariance (ANCOVA) and last-observation-carried-forward (LOCF) methodologies, without multiplicity adjustments, were used to assess changes in continuous measures. Onset of efficacy was defined as the first time point a treatment group showed significant PANSS improvement (assessed days 4, 8, 22, 36, 64, and 92) versus placebo, which was maintained through end point.ResultsA total of 312 subjects met inclusion criterion for this subgroup analysis. After the day 1 injection, mean PANSS total scores improved significantly with PP (all received 234 mg) versus placebo at day 4 (P = 0.012) and day 8 (P = 0.007). After the day 8 injection, a significant PANSS improvement persisted at all subsequent time points in the 234-mg group versus placebo (P < 0.05). PANSS improvements were greater from day 36 through end point in the 156-mg group (P < 0.05) and only at end point in the 39-mg group (P < 0.05). CGI-S and PSP scores improved significantly in the 234-mg and 156-mg PP groups versus placebo at end point (P < 0.05 for both, respectively); improvement in the 39-mg group was not significant. The most common AEs for PP-treated subjects (≥10%, any treatment group) were headache, insomnia, schizophrenia exacerbation, injection site pain, and agitation.ConclusionsIn this markedly to severely ill population, acute treatment with 234 mg PP improved psychotic symptoms compared with placebo by day 4. After subsequent injections, observed improvements are suggestive of a dose-dependent effect. No unexpected tolerability findings were noted.

Paliperidone Extended-Release in Schizoaffective Disorder

This 6-week, double-blind, placebo-controlled study evaluated paliperidone extended-release (ER) as both monotherapy and adjunctive therapy to mood stabilizers and/or antidepressants (MS/ADs) for schizoaffective disorder. Included subjects had a schizoaffective disorder diagnosis; a Positive and Negative Syndrome Scale (PANSS) total score of 60 or higher; a score of 4 or higher on 2 or more of the PANSS items for hostility, excitement, tension, uncooperativeness, or poor impulse control; and prominent mood symptoms (≥16 on the Young Mania Rating Scale and/or the 21-item Hamilton Rating Scale for Depression). Subjects were randomized to 6 mg/d paliperidone ER or placebo with flexible dosing (3-12 mg/d) until day 15. Randomization was stratified by use of MS/AD and study site. The primary analysis outcome was change in PANSS total score at week 6 last observation carried forward end point. A total of 311 subjects received paliperidone ER (n = 216) or placebo (n = 95); 52.0% received MS/AD. The mean (SD) modal dose of paliperidone ER was 8.6 (2.5) mg/d. Greater improvement was observed with paliperidone ER than placebo on mean (SE) PANSS total scores: -20.0 (1.3) and -10.8 (1.9), respectively. Subjects with prominent manic or depressive symptoms showed greater improvement with paliperidone ER versus placebo: mean (SE) Young Mania Rating Scale (-10.6 [0.9] vs -5.7 [1.2], respectively) and 21-item Hamilton Rating Scale for Depression (-10.2 [0.7] vs -6.2 [1.1], respectively). The most common adverse events with paliperidone ER were headache, akathisia, dizziness, insomnia, and dyspepsia. Paliperidone ER improved psychotic and affective symptoms both as monotherapy and as an adjunct to MS/AD. No new safety findings were observed in this population.

Time course of antipsychotic treatment response in schizophrenia: Results from a naturalistic study in 280 patients

ObjectiveTo describe the course of positive and negative symptoms during inpatient treatment and examine remission and response rates under routine clinical care conditions. MethodsTwo hundred and eighty inpatients with schizophrenia (DSM-IV criteria) were assessed with the Positive and Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the symptom–severity component of the consensus criteria (Remission in Schizophrenia Working Group) as a rating of three or less in the relevant PANSS items at discharge, and response as a reduction of at least 20% in the PANSS total score from admission to discharge. ResultsThe mean duration of inpatient treatment was 54.8days. Of the total sample, 78.5% achieved the criteria for response and 44.6% those for remission. Mean PANSS total scores decreased from 72.4 at admission to 52.5 at discharge (p<0.001). A reduction in PANSS total scores was found from visit to visit, up to week 8. The most pronounced decline was observed within the first two weeks of treatment. ConclusionResponse rates were comparable to those found in efficacy studies, and remission rates were slightly higher. This may be explained by differences in the selection and the treatment of patients. Nevertheless, the findings might indicate that a complex naturalistic treatment approach is beneficial in terms of effectiveness.

Paliperidone palmitate, a potential long-acting treatment for patients with schizophrenia. Results of a randomized, double-blind, placebo-controlled efficacy and safety study

We evaluated the efficacy and safety of the investigational long-acting injectable antipsychotic agent paliperidone palmitate (PP) in the treatment of schizophrenia. Patients were randomized to receive gluteal injections of placebo or PP (50 or 100 mg eq., fixed doses), without oral supplementation, on days 1, 8, and 36 (9-wk, double-blind phase) in this phase 2b study. Patients (n=197, intent-to-treat analysis set) were 62% men, mean (s.d.) age 39 (10) yr, with a baseline mean (s.d.) Positive and Negative Syndrome Scale (PANSS) total score of 87.0 (12.5). Mean (s.d.) PANSS total scores showed significant improvement at endpoint (primary measure) for both the PP 50 mg eq. [-5.2 (21.5)] and PP 100 mg eq. [-7.8 (19.4)] groups, vs. placebo [6.2 (18.3)] (p0.001, each dose vs. placebo). This improvement was detected by day 8 and maintained to endpoint (p0.011) for both doses. In the safety analysis set (n=247), fewer PP-treated patients (2%) discontinued for treatment-emergent adverse events vs. placebo-treated (10%). Rates of treatment-emergent extrapyramidal syndrome-related adverse events were comparable between active treatment and placebo, with the exception of parkinsonism-related disorders (50 mg eq. 5%, 100 mg eq. 8%, placebo 1%). Results of other safety measures suggest PP to be generally well-tolerated. Throughout the study, investigators rated injection-site pain as absent (56-71%), mild (24-39%), moderate (2-12%), or severe (0-2%). PP (50 and 100 mg eq. doses) administered as a gluteal intramuscular injection was efficacious and generally tolerated in these patients with acute symptomatic schizophrenia.

Effectiveness and tolerability of long-acting risperidone: A 9-month open-label extension of a 12-week switching study from oral antipsychotics

Objectives. The aim of this non-randomized, single-arm, multi-center, 9-month extension study was to evaluate the maintained efficacy and tolerability of long-acting risperidone injection when we switched to it from previous oral antipsychotics in symptomatically stable patients with schizophrenia or other psychotic disorders. Methods. A total of 98 patients who had completed a previous 12-week acute phase study were included. Efficacy and tolerability were assessed with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), and Extrapyramidal Symptom Rating Scale (ESRS). Results. The remission rate of 77.6% (76/98) at baseline and 57.1% (56/98) at the end of the study. Of patients who were in remission at baseline, 65.8% (50/76) maintained their remission state until the end. The symptom worsening rate was relatively low (11.1%), and there was no aggravation in mean PANSS total and subscale scores. Spontaneous treatment-emergent adverse events (TEAE) were reported by 21 (21.4%) patients, and most commonly reported adverse events were extrapyramidal symptoms (N=6, 6.1%) and insomnia (N=4, 4.1%). Extrapyramidal symptoms were significantly improved. Conclusions. Switching to long-acting risperidone injection from oral antipsychotics was a safe and well-tolerated strategy for maintaining clinical stability in symptomatically stable patients with schizophrenia.

Long-Term Improvement in Efficacy and Safety After Switching to Ziprasidone in Stable Outpatients with Schizophrenia

The long-term efficacy and tolerability of treatment with ziprasidone following a switch from prior antipsychotics was evaluated in outpatients with schizophrenia or schizoaffective disorder in three open-label, flexible-dose, 1-year extension studies. These studies enrolled completers of 6-week trials in which subjects were switched to ziprasidone from conventional antipsychotics, olanzapine, or risperidone. Identical study designs and the small number of patients entering the extensions supported pooling of the data. Of 185 pooled subjects entering the extension studies, 72 completed 58 weeks of treatment. Median treatment duration was 34.6 weeks; median dose was 120 mg/day at endpoint. The intent-to-treat population showed significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores (-4.3 [P< or =.01]), PANSS negative scores (-2.4 [P< or =.0001]), and Clinical Global Impression of severity score (-0.3 [P< or =.001]). Completers showed significant improvement in mean PANSS total scores (-10.2 [P<.0001]), PANSS positive scores (-2.7 [P< .0001]), PANSS negative scores (-2.7 [P< .001]), and Clinical Global Impression of severity scores (-0.6 [P< .0001]). Ziprasidone was well tolerated, and patients demonstrated significant improvement in metabolic parameters and in all movement disorder assessments. Insomnia and somnolence were the only adverse events with an incidence >10% in pooled subjects. No subject had a corrected QT interval > or =500 msec.

Remission in schizophrenia: Results from a 1-year study of long-acting risperidone injection

Purpose Although treatment advances have improved outcomes in schizophrenia, definitions of remission and recovery are still evolving. Recently proposed criteria for remission (mild or less on multiple core-symptom ratings for at least 6 months) have been applied to a 1-year study of long-acting risperidone injection. Methods In a 50-week, open-label trial, stable patients with schizophrenia or schizoaffective disorder who received long-acting risperidone injection every 2 weeks were assessed using the Positive and Negative Syndrome Scale (PANSS). Remission criteria for the PANSS were applied; global illness severity (Clinical Global Impressions) and patient-rated health status (36-Item Short-form Health Survey) were measured. Results Groups were identified by initial remission status (excluding the time component). Although considered clinically “stable,” 68.2% (394 / 578) did not meet the symptom-severity component of remission criteria at baseline. Following long-acting, injectable risperidone treatment, 20.8% (82) of nonremitted patients achieved symptom remission for at least 6 months, with significant decreases in mean PANSS total and cluster scores ( P < 0.0001) and significantly improved patient-rated health status ( P < 0.0001). Percentages rated as not ill, very mild, or mild increased from 39% to 88%. Among 31.8% (184 / 578) of patients meeting the symptom-severity component of remission criteria at baseline, 84.8% (156) maintained these criteria at endpoint. Conclusions Among previously “stable,” nonremitted patients, many achieved symptom remission after long-acting, injectable risperidone treatment, with significant improvements in multiple symptom domains and patient-rated health status. These results warrant further study as these remission criteria may represent a meaningful clinical endpoint and an important step towards functional recovery.