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This study aimed to investigate the benefit of Bonebridge devices in patients with single-sided deafness.
Five patients with single-sided deafness who were implanted with Bonebridge devices were recruited in a single-centre study. Participants’ speech perception and horizontal sound localisation abilities were assessed at 6 and 12 months post-operatively. Speech intelligibility in noisy environments was measured in three different testing conditions (speech and noise presented from the front, speech and noise presented from the front and contralateral (normal ear) side separately, and speech presented from the ipsilateral (implanted Bonebridge) side and noise from the contralateral side). Sound localisation was evaluated in Bonebridge-aided and Bonebridge-unaided conditions at different stimuli levels (65, 70 and 75 dB SPL).
All participants showed a better capacity for speech intelligibility in quiet environments with the Bonebridge device. The speech recognition threshold with the Bonebridge device was significantly decreased at both short- and long-term follow up in the speech presented from the ipsilateral (implanted Bonebridge) side and noise from the contralateral side condition (p < 0.05). Additionally, participants maintained similar levels of sound localisation between the Bonebridge-aided and unaided conditions (p > 0.05). However, the accuracy of localisation showed some improvement at 70 dB SPL and 75 dB SPL post-operatively.
The Bonebridge device provides the benefit of improved speech perception performance in patients with single-sided deafness. Sound localisation abilities were neither improved nor worsened with Bonebridge implantation at the follow-up assessments.
To evaluate the effect of the burden of Staphylococcus aureus colonization of nursing home residents on the risk of S. aureus transmission to healthcare worker (HCW) gowns and gloves.
Multicenter prospective cohort study.
Setting and participants:
Residents and HCWs from 13 community-based nursing homes in Maryland and Michigan.
Residents were cultured for S. aureus at the anterior nares and perianal skin. The S. aureus burden was estimated by quantitative polymerase chain reaction detecting the nuc gene. HCWs wore gowns and gloves during usual care activities; gowns and gloves were swabbed and then cultured for the presence of S. aureus.
In total, 403 residents were enrolled; 169 were colonized with methicillin-resistant S. aureus (MRSA) or methicillin-sensitive S. aureus (MSSA) and comprised the study population; 232 were not colonized and thus were excluded from this analysis; and 2 were withdrawn prior to being swabbed. After multivariable analysis, perianal colonization with S. aureus conferred the greatest odds for transmission to HCW gowns and gloves, and the odds increased with increasing burden of colonization: adjusted odds ratio (aOR), 2.1 (95% CI, 1.3–3.5) for low-level colonization and aOR 5.2 (95% CI, 3.1–8.7) for high level colonization.
Among nursing home patients colonized with S. aureus, the risk of transmission to HCW gowns and gloves was greater from those colonized with greater quantities of S. aureus on the perianal skin. Our findings inform future infection control practices for both MRSA and MSSA in nursing homes.
Dietary chitosan (CS) supplementation could improve the growth rate, small intestinal morphology, nutrients apparent digestibility and digestive enzyme activities in pigs, broiler chickens, rats and fish, whereas no data has been reported about the effect of CS on the growing Huoyan geese. Therefore, this study was designed to investigate the effects of CS on growth rate, small intestinal morphology, nutrients apparent utilization and digestive enzyme activities of growing Huoyan geese. Three hundred and twenty (28 days of age, gender balance) Huoyan geese were randomly divided into control, CS100, CS200 and CS400 groups (based on BW) with 20 geese per pen and 4 replicates pen per group, and the feeding experiment lasted for 4 weeks. The 4 diets contained 0, 100, 200 and 400 mg CS per kg feed, respectively. The results showed that CS200 groups had higher average daily gain, final BW, apparent utilization of DM and CP, and lower feed/gain ratio compared with the control group (P < 0.05). Meanwhile, CS100 and CS200 groups had higher villus height, villus height/crypt depth ratio and lower crypt depth in duodenum and jejunum than those in the control group (P < 0.05). The geese in CS100 and CS200 groups had higher villus height, villus height/crypt depth ratio and lower crypt depth of ileum compared with those in control and CS400 groups (P < 0.05). In addition, compared with the control group, CS200 group has higher trypsin activities and lower lipase activities in duodenal, jejunal and ileal contents (P < 0.05). The results suggested that addition of 200 mg/kg CS had positive effects on growth rate, small intestinal morphology, nutrients apparent utilization and digestive enzyme activities of growing Huoyan geese.
Asenapine is indicated in adults for acute treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder with or without psychotic features. We report the safety, tolerability, and efficacy of asenapine in patients with bipolar I disorder completing up to 52 weeks of treatment.
Patients completing either of two 3-week efficacy trials and a 9-week double-blind extension were eligible for this 40-week double-blind extension. Patients in the 3-week trials were randomized to flexible-dose asenapine (5 or 10 mg BID), placebo, or olanzapine (5-20 mg QD; included for assay sensitivity only). Patients entering the extension continued their preestablished treatment; those originally randomized to placebo received flexible-dose asenapine (placebo/asenapine, 5 or 10 mg BID). Safety and tolerability endpoints included adverse events (AEs), extrapyramidal symptoms, laboratory values, and anthropometric measures. Efficacy was measured as the change in Young Mania Rating Scale (YMRS) total score from 3-week trial baseline to week 52; the placebo/asenapine group was included in the safety analyses.
Incidence of treatment-emergent AEs was 71.9%, 86.1%, and 79.4% with placebo/asenapine, asenapine, and olanzapine, respectively. The most frequent AEs included headache and somnolence (placebo/asenapine); insomnia, sedation, and depression (asenapine); and weight gain, somnolence, and sedation (olanzapine). Mean ± SD changes in YMRS score at week 52 among observed cases in the intent-to-treat population were -28.6±8.1 for asenapine and -28.2±6.8 for olanzapine.
In this 52-week study, asenapine was well tolerated and long-term maintenance of efficacy was supported in patients initially presenting with bipolar mania.
Asenapine is indicated in adults for acute treatment of schizophrenia and bipolar I disorder. We describe the efficacy and tolerability of adjunctive asenapine in bipolar patients showing incomplete response to lithium or valproate monotherapy.
In a 12-week core study, patients were randomized to flexible-dose asenapine (5 or 10 mg BID) or placebo as an adjunct to continued mood stabilizer therapy. Patients completing the core study without protocol violations could enter a 40-week extension. Changes from core study baseline on the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS) total scores were assessed at week 3 of the core study and at week 52 in the extension. Efficacy in the core study was assessed using ANCOVA with LOCF to impute missing data. The extension was not powered for statistical comparisons; descriptive statistics were employed.
The intent-to-treat population comprised 318 patients (asenapine, 155; placebo, 163) in the core study and 71 (38; 33) in the extension. Mean±SD changes at week 3 with asenapine and placebo, respectively, were -9.7±10.1 versus -7.7±9.6 (P=0.0257) on YMRS and -2.8±7.2 versus -2.2±6.8 (P=0.3684) on MADRS. Mean±SD changes at week 52 with asenapine and placebo were -17.2±13.7 versus -19.7±11.8 on YMRS and -3.3±9.8 versus -3.9±7.7 on MADRS. The incidence of treatment-emergent AEs with asenapine and placebo was 73% and 69% in the core study, 78% and 69% in the extension.
Asenapine was effective as an adjunct to mood stabilizer in bipolar I disorder and was well tolerated.
Assess clinical and functioning treatment outcomes of risperidone long-acting injection (RLAI) versus oral antipsychotics for patients participating in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) in Spain.
e-STAR is a 2-year, multi-national, prospective, observational study of patients with schizophrenia who were initiated on RLAI or an oral antipsychotic. Data were collected retrospectively (1-year) and prospectively every three months (2 years). Outcomes included clinical effectiveness measured by Clinical Global Impression of Illness Severity (CGI-S) and patient functioning assessed by Global Assessment of Functioning (GAF) scale. Clinical and functional outcomes are analyzed using a linear mixed model controlling for age, gender, disease duration, baseline hospitalization status and antipsychotic treatment patterns. Results presented are based on the complete e-STAR data from Spain.
1,622 patients (63.6% male, mean age 38.4±11.2 years) participated in e-STAR from Spain, 1,345 were initiated on RLAI and 277 on oral antipsychotics. RLAI treated patients had significantly longer disease duration (12.6±9.5 years vs. 10.9±9.7, p<0.01) than those treated with oral antipsychotics. During the 2-year study, clinical symptoms and functioning improved in both groups. As revealed by the mixed-model regression, RLAI patients, compared to oral patients, had significantly greater improvement on CGI-S scores (-1.10 vs. -0.88, p<0.02) and GAF scores (16.4 vs. 14.6, p<0.03). Baseline hospitalization status and disease duration were significant explanatory variables in the mixed model regression.
This 2-year, prospective, observational study showed that compared to oral antipsychotics, RLAI treatment was associated with greater improvement in clinical symptoms and functioning in patients with schizophrenia.
Individuals with co-occurring disorders have higher levels of psychological distress and poorer psychosocial functioning, as compared with individuals with substance dependence only. Studies identified substance abuse as a risk factor, which increases the likelihood that an individual with mental disorders may become violent.
To examine the gender differences in drug-related problems and predictors of recidivism among a sample of 1,444 offenders with co-morbid drug abuse and mental disorders participating in California's Proposition 36.
Characteristics and problem severity in multiple key life areas were assessed at intake using Addiction Severity Index, and drug treatment participation, mental health diagnoses and arrests were based on official records.
Women demonstrated greater problem severity than men in family relationships, health, psychological health, and sexual and physical abuse history. Men on the other hand had greater criminal history, high rates of attention disorder, and psychotic disorder. Logistic regression analyses showing that for the combined sample, male, young age, cocaine use (relative to methamphetamine), drug abuse severity, methadone treatment, arrest history and fewer prior treatment history were associated with higher recidivism at 12-month follow-up; lower education, cocaine use, and arrest history were related to women's recidivism, while young age, outpatient treatment, and arrest history were predictors of men's recidivism.
Although the specific type of mental disorder did not seem to be predictive of recidivism, the high rates of mental health disorder and arrest of this population is problematic. Intervention strategies taking into consideration gender-specific problems and needs can improve outcomes for both.
The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice.
Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n = 1345) or a new oral antipsychotic (AP) (n = 277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review.
At 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p < 0.0001) and reduction in Clinical Global Impression Severity scores (−1.14 for RLAI versus −0.94 for APs, p = 0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p < 0.05) and days (18.74 versus 13.02, p < 0.01) of hospitalizations at 24 months than oral AP patients.
This 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.
Asenapine and olanzapine reduced persistent negative symptoms (PNS) of schizophrenia in 2 double-blind, randomized 26-week studies and subsequent 26-week extensions; superiority of asenapine over olanzapine was observed in neither core study and only 1 extension.
Further explore the efficacy of asenapine on PNS using pooled data.
Demonstrate superiority of asenapine over olanzapine on PNS.
Core study participants were randomized to twice-daily asenapine 5 or 10 mg or once-daily olanzapine 5–20 mg; extension participants continued existing treatment. Changes from core study 16-item Negative Symptom Assessment (NSA-16) Scale baseline at Weeks 26 and 52 were estimated using MMRM.
Of 949 treated participants (asenapine, 485; olanzapine, 464), 613 (277; 336) completed the core studies and 412 (170; 242) completed the extensions. Discontinuation due to lack of therapeutic effect was significantly greater with asenapine vs olanzapine for the first 26 weeks (13.6% vs 7.3%, p = 0.0016) and during the extension (5.5% vs 2.1%, p = 0.0458) for core and extension study participants, respectively. Between-group differences in least squares mean ± SE NSA-16 score change from core study baseline were significantly greater with asenapine at Week 52 for core (-14.6 ± 0.8 vs -12.6 ± 0.7; p = 0.0497) and extension (-16.5 ± 0.9 vs -13.6 ± 0.7; p = 0.0083) participants, but were not significant at Week 26.
In pooled analyses, asenapine and olanzapine reduced PNS, with statistical superiority of asenapine observed at Week 52 but not Week 26. These results should be interpreted in view of the fact that participants who entered the extensions did so without rerandomization.
Aripiprazole has demonstrated efficacy for the treatment of paediatric patients (10–17 years) with a manic or mixed episode associated with bipolar I disorder in a clinical trial that utilised the Young Mania Rating Scale (YMRS) Total score as the primary outcome measure.
This analysis evaluated the profile of discrete symptom response using the YMRS and other measures.
Post-hoc analysis of individual items of the YMRS and the parent or subject version of the General Behaviour Inventory (GBI) Mania and Depression scales using data from a 4-week, double-blind, randomised trial that compared aripiprazole (10 or 30 mg/day, n = 197) with placebo (n = 99).
In total, 296 patients were randomised; 80% completed the study. Significant decreases at Week 4 (p < 0.05) were seen in eight YMRS items: elevated mood, increased motor activity/energy, need for sleep, irritability, speech (rate and amount), language/thought disorder, abnormal thought content and disruptive/aggressive behaviour. For the GBI, effect sizes for parent-reported mania items were medium to large (for example, 0.41 for ‘depressed but high energy’ to 0.78 for ‘rage combined with unusually happy’) but were consistently small on subject self-reported items of mania and depression and, for the overall scale, had the poorest agreement with clinician ratings.
Aripiprazole demonstrated improvements in some of the more troublesome symptoms of paediatric patients with bipolar I disorder experiencing an acute manic or mixed episode. Of note, irritability and aggression showed large treatment effects on both clinician and parent-reported measures, but less so for subject-reported measures.
The relative effect of the atypical antipsychotic drugs and conventional agents on neurocognition in patients with early-stage schizophrenia has not been comprehensively determined.
The present study aimed to assess the cognitive effects of atypical and conventional antipsychotic drugs on neurocognition under naturalistic treatment conditions.
In a 12 months open-label, multicenter study, 698 patients with early-stage schizophrenia (< 5 years) were monotherapy with chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine or aripiprazole. Wechsler Memory Scale--Revised Visual Reproduction Test, Wechsler Adult Intelligence Scale Revised Digit Symbol Test and Digit-span Task Test, Trail Making Tests Part A and Part B, and Wisconsin Card Sorting Test were administered at baseline and 12 months follow-up evaluation. The primary outcome was change in a cognitive composite score after 12 months of treatment.
Compared with scores at baseline, the composite cognitive test scores and individual test scores had significant improvement for all seven treatment groups at 12-month follow-up evaluation (all p-values ≤ 0.013). However, olanzapine and quetiapine provided greater improvement than that provided by chlorpromazine and sulpiride in the composite score, processing speed and executive function (all p-values ≤ 0.045).
Both conventional and atypical antipsychotic medication long-term maintenance treatment can benefit congitive function in patients with early-stage schizophrenia, but olanzapine and quetiapine may be superior to chlorpromazine and sulpiride in improving some areas of neurocognitive function.
We sought to explore whether obstetric complications (OCs) are more likely to occur in the presence of familial/genetic susceptibility for schizophrenia or whether they themselves represent an independent environmental risk factor for schizophrenia.
The presence of OCs was assessed through maternal interview on 216 subjects, comprising 36 patients with schizophrenia from multiply affected families, 38 of their unaffected siblings, 31 schizophrenic patients with no family history of psychosis, 51 of their unaffected siblings and 60 normal comparison subjects. We examined the familiality of OCs and whether OCs were commoner in the patient and sibling groups than in the control group.
OCs tended to cluster within families, especially in multiply affected families. Patients with schizophrenia, especially those from multiply affected families, had a significantly higher rate of OCs compared to normal comparison subjects, but there was no evidence for an elevated rate of OCs in unaffected siblings.
Our data provides little evidence for a link between OCs and genetic susceptibility to schizophrenia. If high rates of OCs are related to schizophrenia genes, this relationship is weak and will only be detected by very large sample sizes.
Evaluate impact of risperidone long-acting injection (RLAI) versus oral antipsychotics on hospitalization outcomes for patients in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) in Spain.
e-STAR is a 2-year, multi-national, prospective, observational study of patients with schizophrenia who initiated on RLAI or an oral antipsychotic. Hospitalization outcomes including number of hospitalizations and number of days in hospital were collected retrospectively (1-year) and prospectively (2 years). Changes in hospital stays and days in hospital were compared between RLAI and oral patients using linear mixed model controlling for age, gender, disease duration, and baseline antipsychotic use patterns.
1,622 patients (63.6% male, mean age 38.4±11.2 years) participated in e-STAR from Spain, 1,345 initiated on RLAI and 277 on oral antipsychotics. RLAI patients had significantly longer disease duration (12.6±9.5 years vs. 10.9±9.7 in oral patients, p<0.01). Average hospital stay at baseline was 5 days longer for RLAI than oral patients. During the study, both treatments showed reductions in mean number of hospitalizations and mean number of days in hospital. Based on the mixed-model regression, RLAI patients, compared to oral patients, had a significantly greater reduction in mean number of hospitalizations (-0.28 vs. -0.18 in followup-year1 and -0.37 vs. -0.20 in followup-year2, p<0.05) and mean number of days in hospital (-17.23 vs. -12.96 in followup-year1 and -18.75 vs. -12.99 in followup-year2, p<0.01).
This 2-year, prospective, observational study showed that compared to oral antipsychotics, RLAI treatment was associated with greater reduction in hospital stays and days in hospital in patients with schizophrenia.
Previously the GABA(A) receptor beta-2 subunit gene GABRB2 was found to be associated with schizophrenia (SCZ). for SNPs and haplotypes in GRBRB2, the associations with bipolar disorder (BPD), the functional consequences on GABRB2 expression and their relationship to demographic and clinical characteristics in BPD and SCZ remain to be elucidated.
Case-control analysis was performed for association study of GABRB2 with BPD, and its mRNA expression in postmortem BPD brains was examined using quantitative real-time PCR. Quantitative trait analysis was subsequently employed to assess the covariate effects of demographic and clinical characteristics on genotypic correlation of GABRB2 expression in SCZ and BPD.
Significant association of GABRB2 with BPD and reduction in GABRB2 mRNA expression in BPD brains were observed in the present study. Duration of illness (DOI) was found to be a significant covariate for the correlation of the disease-associated SNPs rs1816071, rs1816072 and rs187269 with GABRB2 expression in both SCZ and BPD. for individuals with homozygous major genotypes of these SNPs, while GABRB2 expression increased with age in the controls, it decreased with DOI and age in SCZ, and with DOI in BPD. with age of onset as covariate, these three SNPs were significantly correlated with antipsychotic dosage in SCZ.
These results have thus revealed correlations of GABRB2 SNPs and expression not only with the occurrence of SCZ and BPD, but also with the clinical characteristics of patients, therefore providing support for a shared etiological role played by the gene in both diseases.
GABRB2, the gene for β2 subunit of the gamma-aminobutyric acid type A (GABAA) receptor, is known to display two splicing isoforms in the brain, namely β2L containing Exon 10 and β2S devoid of Exon 10. Previously, the expressions of these isoforms were correlated with both schizophrenia and various sequence polymorphisms of the gene. in the present study, a series of deletions made on Intron 9 of a minigene construct affected the expression of Exon 10, and generated additional splicing variations suggesting the existence of additional splicing variants of β2subunit. A search among brain cDNAs uncovered the two novel short forms: β2S1which is devoid of Exons 10 and 11 and bears an extended Exon 9, and β2S2 which is devoid of Exon 10 and bears a shortened Exon 11.Real-time quantitative polymerase chain reaction, performed with a cohort of 31 schizophrenics, 30 bipolar disorder and 31 controls of US population, showed that the level of β2S2 was significantly decreased in bipolar disorder, and marginally decreased in schizophrenia, while β2S1 was marginally increased in both of these psychotic disorders. Significant genotypic effects of rs1816071, rs1816072 and rs187269 on β2S2 level were observed in male schizophrenic and bipolar patients. These findings pointed to the neighborhood of Exon 10 as an alternate-splicing hot-spot, and underlined the relevance of β2 subunit isoforms to the etiology of psychotic disorders.
Injection drug use is a major route of HIV transmission in China yet relatively little is known about why so few injection drug users utilize free HIV testing services. This study aim to examine barriers to HIV testing/ VCT service utilization among injection drug users in Shanghai, China.
Utilizing mixed methods, we analyzed data from a survey of 540 compulsory drug abuse treatment patients and data from focus groups with 70 service providers and patients.
Only 24.4% of patients expressed willingness to be tested for HIV. Willingness to be tested was associated with younger age and more positive attitudes toward condom use. Patients reported several barriers to utilization of voluntary HIV testing services, including lack of information about this services, perceptions of no- or low-risk for HIV infection, fear of positive results, and the stigma or discrimination that may be experienced by oneself or family. Having limited skills related to HIV counseling was reported by service providers as the primary barrier to encouraging patients to utilize HIV testing/VCT services.
Special intervention programs targeting injection drug users, their family members, and service providers may increase HIV testing in China.
Previous studies have shown that the polymorphisms in COMT gene and environmental factors affect the risk of drug dependence, but there’s no research shown in relapse of heroin dependence, and the mechanism underlying remains uncertain.
Examine the interaction between allelic variants of the catechol-O- methlytransferase (COMT) gene and environmental factors (encountering drug-related environmental situations, social support) in contribution to relapse in heroin dependence.
Construct the gene-environment interaction model in order to understand the mechanism for relapse in heroin dependence.
The 249 heroin dependent subjects who followed up at one year after abstinent by using the natural history interview (NHI), social support rateing Scale (SSRS), and other questionnaires were genotyped for eight tagging single nucleotide polymorphisms (SNP) on the COMT gene. General Multifactor Dimensionality Reduction (GMDR) was used to construct the gene-environment interaction model which impacting relapse in heroin dependence.
The relapse group had higher frequencies of encountering drug-related environment (EDE) and G allele and GG genotype frequencies on COMT gene rs4680 locus and less Social Support Scale scores than that in the abstinence group. Logistic regression analysis showed that encountering more drug-related environment and GG genotype carriers were the risk factors for relapse in heroin dependence. GMDR analysis showed that the COMT gene was interact with the frequency of EDE and social support level to impact the relapse in heroin dependence.
Gene-environment interaction between COMT gene and the frequency of EDE and social support were related to heroin dependence relapse.
To determine whether early manic symptom improvement predicts outcome in bipolar I disorder patients experiencing manic or mixed episodes.
Pooled data from two 3-week trials; asenapine (5 or 10 mg BID; n = 372), olanzapine (5-20 mg QD; n = 391), or placebo (n = 197). Early improvement (YMRS total score changes from baseline ≥15%, ≥20%, and ≥25%) was assessed at days 2, 4, and 7. Associations between early improvement and week 3 outcomes (YMRS response [≥50% total score reduction] and remission [total score ≤12]) were calculated using Fisher's exact tests; odds ratios classified their relative strength. Sensitivity (SN), specificity (SP), and positive (PPV) and negative (NPV) predictive values were calculated as previously described (J_Clin_Psychiatry_2009;70:344–353).
Early improvement was strongly associated with positive outcomes. the earliest positive associations across all cutoffs occurred with asenapine at day 2 (response, all P < 0.04; remission, all P < 0.007), olanzapine at day 4 for response (all P < 0.02) and day 2 for remission (all P < 0.002), and placebo on day 7 (response, all P < 0.003; remission, all P ≤ 0.0005). Odds ratios were higher for asenapine (1.8–9.1) than olanzapine (1.4–3.5) and placebo (1.3–8.0). Respective day 4 remission values for SN, SP, PPV, and NPV at the ≥ 15% cut-off were 80%, 58%, 48%, and 85% for asenapine; 76%, 43%, 49%, and 71% for olanzapine; and 50%, 67%, 31%, and 82% for placebo.
Early improvement was strongly associated with week 3 response and remission; high NPVs indicated little chance of stable remission in the absence of early improvement.
Assess the incidence and time-course of somnolence in placebo- and active-controlled asenapine schizophrenia and bipolar I disorder (BD) trials.
Data were from schizophrenia (4 short-term [6wk]; 3 long-term [26-52wk]) and BD (2 short-term [3wk]; one 12-wk adjunct therapy to mood stabilizers) trials. Data were pooled across asenapine doses (5or10 mg BID); active controls were risperidone 3 mg BID, olanzapine 5-20 mg QD, and haloperidol 4 mg BID.
For schizophrenia, incidence of somnolence was higher with active treatment than placebo in short-term trials; (asenapine,13.1%; placebo, 6.9%; active controls, 5–20%); and comparable for asenapine and olanzapine in long-term trials; (asenapine,18.4–18.5%; olanzapine, 19.6–21.1%); severe somnolence was infrequent (0–8%). Somnolence onset (median [days]) occurred early in short-term (asenapine, 2.0; placebo, 7.0; active controls, 2–6) and long-term (asenapine, 9.0; olanzapine, 7.5–9.0) trials; median somnolence duration (days) was relatively brief in short-term (asenapine,15.0; placebo, 4.5; active controls; 3.0–22.5) and long-term (asenapine, 22.0–25.0; olanzapine, 21.0–25.0) trials. For BD, incidence of somnolence was higher with active treatment than placebo in short-term (asenapine, 23.8%; placebo, 6.4%; olanzapine, 26.4%) and adjunctive therapy (asenapine, 24.1%; placebo, 10.2%) trials; severe somnolence was infrequent (0–3%). Somnolence onset (median [days]) occurred early in short-term (asenapine, 1.0; placebo, 2.0; olanzapine, 1.0) and adjunctive therapy (asenapine,1.5; placebo,2.0) trials; median somnolence duration (days) was brief in short-term (asenapine, 7.0; placebo, 5.0; olanzapine, 8.5) and adjunctive therapy (asenapine,12.5; placebo, 7.0) trials.
The analyses show, on average, an early onset and a limited duration of treatment-emergent somnolence with asenapine, which may be clinically useful in certain clinical situations.