Asenapine In Patients Research Articles

Sensory evaluation of the bitterness of asenapine using D-sorbitol pretreatment: single-blind, placebo-controlled, crossover trial

BackgroundAntipsychotics are essential in the acute treatment of and maintenance therapy for schizophrenia, but medication adherence and long-term treatment continuity are needed to maximize their effectiveness. Each antipsychotic has various side effects, which may affect adherence. Some patients with schizophrenia are reluctant to take asenapine because of its unique oral-related side effects, such as the bitter taste caused by sublingual administration. Our previous basic research found that D-sorbitol lowered the bitterness parameters of the taste sensors. However, whether D-sorbitol has the same effect in patients remains unclear. Therefore, using a D-sorbitol solution, we aim to evaluate changes in the bitterness of asenapine among patients with schizophrenia.MethodsIn this single-blind, placebo-controlled, crossover trial, we plan to recruit 20 adult patients with schizophrenia spectrum disorder who take sublingual asenapine tablets. The participants will be divided into two groups (n = 10 each). Each group will be given a D-sorbitol or placebo solution on the first day for rinsing before taking the sublingual asenapine tablets. After a 1-day interval, the participants will rinse their mouths again with a different liquid. Questionnaires regarding changes in taste and the willingness to continue asenapine will be conducted before the start of the study and after each rinse. The primary and secondary end points will be a taste evaluation of bitterness, and the willingness to continue asenapine, respectively. Differences in questionnaire scores between the D-sorbitol and placebo solutions will be calculated and analyzed using a McNemar test.DiscussionThis study aims to determine the efficacy of D-sorbitol in masking the bitter taste of asenapine. To our knowledge, it is the first intervention study using D-sorbitol for bitter taste of asenapine in patients with schizophrenia. Evidence of the efficacy of D-sorbitol could result in D-sorbitol pretreatment being an easy and inexpensive means of improving adherence to asenapine.Trial registrationThis study was registered in the Japan Registry of Clinical Trials jRCTs041210019, on May 14, 2021. Ethics approval was obtained from the Nagoya University Clinical Research Review Board.

The Influence of Long-Term Treatment with Asenapine on Liver Cytochrome P450 Expression and Activity in the Rat. The Involvement of Different Mechanisms.

Therapy of schizophrenia requires long-term treatment with a relevant antipsychotic drug to achieve a therapeutic effect. The aim of the present study was to investigate the influence of prolonged treatment with the atypical neuroleptic asenapine on the expression and activity of rat cytochrome P450 (CYP) in the liver. The experiment was carried out on male Wistar rats. Asenapine (0.3 mg/kg s.c.) was administered for two weeks. The levels of CYP mRNA protein and activity were determined in the liver and hormone concentrations were measured in the pituitary gland and blood serum. Asenapine significantly decreased the activity of CYP1A (caffeine 8-hydroxylation and 3-N-demethylation), CYP2B, CYP2C11 and CYP3A (testosterone hydroxylation at positions 16β; 2α and 16α; 2β and 6β, respectively). The neuroleptic did not affect the activity of CYP2A (testosterone 7α-hydroxylation), CYP2C6 (warfarin 7-hydroxylation) and CYP2E1 (chlorzoxazone 6-hydroxylation). The mRNA and protein levels of CYP1A2, CYP2B1, CYP2C11 and CYP3A1 were decreased, while those of CYP2B2 and CYP3A2 were not changed. Simultaneously, pituitary level of growth hormone-releasing hormone and serum concentrations of growth hormone and corticosterone were reduced, while that of triiodothyronine was enhanced. In conclusion, chronic treatment with asenapine down-regulates liver cytochrome P450 enzymes, which involves neuroendocrine mechanisms. Thus, chronic asenapine treatment may slow the metabolism of CYP1A, CYP2B, CYP2C11 and CYP3A substrates (steroids and drugs). Since asenapine is metabolized by CYP1A and CYP3A, the neuroleptic may inhibit its own metabolism, therefore, the plasma concentration of asenapine in patients after prolonged treatment may be higher than expected based on a single dose.

Rapidity of Action, Effectiveness and Adherence to Treatment with Asenapine: a Real-world, Observational Study

Asenapine (ASE) is a second-generation antipsychotic with a unique pharmacological profile, that was recently approved for the treatment of moderate/severe manic episodes (ME). Real-world data on rapidity of action in inpatient settings are lacking. 1) rating scale variation after 7 days (T0-T1) of treatment with ASE in patients hospitalized for ME during Bipolar I Disorder or a Schizoaffective Disorder 2) follow-up on continuity of treatment at 6 months Determination of short-term effects of ASE and continuity of treatment in an observational, real-world study. All inpatients who met DSM-IV-TR criteria for ME treated with ASE were recruited in the 2 years after the drug was available. YMRS and BPRS were administered at T0 and T1. 6 months follow-up data were collected from patients taking ASE at discharge. The mean total YMRS score decreased by 12.6 (SD ±10.3; t(17)=5.2, p<.005), implying a mean 37.8% improvement. A statistically significant reduction was observed for all YMRS items, except for 'sexual interest”. The mean total BPRS score decreased by 17.2 (SD ±14.9; t(17)=4.9, p<.005). A statistically significant reduction was observed for several items, including 'conceptual disorganization”, 'grandiosity”, 'unusual thought content”, 'excitement”. At hospital discharge, ASE was confirmed in 55% of patients, 18% of which were still taking the drug at 6 months: lack of efficacy and poor adherence were found to influence continuity of treatment rather than specific side effects. ASE is rapidly effective in the first week of treatment, but is subject to a high discontinuation rate on the long term.

Asenapine prescribing patterns in the treatment of manic in- and outpatients: Results from the MANACOR study

BackgroundAsenapine is the most recent compound that has been FDA- and EMA-approved for treatment of mania. Its efficacy and safety have been assessed in placebo-controlled trials, but little is known about its performance in routine clinical conditions. In this study, we compared features of patients treated with adjunctive asenapine or other adjunctive antipsychotics and the costs of the treatment. MethodsA combined prospective and retrospective data collection and analysis was conducted from January 2011 to December 2013 following a clinical interview and assessment of manic and depressive symptoms (YMRS, HDRS-17), clinical state (CGI-BP-M), psychosocial functioning (FAST), sexual dysfunction (PRSexDQ) and health resource costs associated with treatment with adjunctive asenapine versus other adjunctive antipsychotics. ResultsHundred and fifty-two patients from different university hospitals were included. Fifty-three patients received adjunctive asenapine and 99 received other adjunctive antipsychotics concomitantly to mood stabilizers. Considering inpatients, those treated with adjunctive asenapine presented a significantly less severe manic episode (P=0.001), less psychotic symptoms (P=0.030) and more comorbid personality disorder (P=0.002). Regarding outpatients, those treated with adjunctive asenapine showed significantly less severe manic episode (P=0.046), more previous mixed episodes (P=0.013) and more sexual dysfunction at baseline (P=0.036). No significant differences were found in mean total costs per day. ConclusionClinicians tended to use adjunctive asenapine in patients with less severe manic symptoms but more complex clinical profile, including more mixed episodes in the past, concomitant personality disorder, and sexual problems. Treatment with adjunctive asenapine was not associated with higher costs when compared to other options.

Weight Change and Metabolic Effects of Asenapine in Patients With Schizophrenia and Bipolar Disorder

To describe weight changes and metabolic effects of asenapine compared with placebo and olanzapine in adults. Post hoc analyses were performed using data from 17 asenapine trials (13 schizophrenia and 4 bipolar mania trials) with placebo (5-10 mg twice daily; n = 1,748; 1-6 weeks) and/or olanzapine (5-20 mg, once daily; n = 3,430; 3-100 weeks). Data were pooled based on treatment into placebo-controlled and olanzapine-controlled trials. For trials with placebo and olanzapine treatment groups, the asenapine population was included in both pools. Changes from baseline for weight, body mass index, and fasting lipid and glucose levels were determined. The Medical Dictionary for Regulatory Activities was used to define metabolic adverse events. Mean (standard error [SE]) weight change was greater with asenapine than with placebo (1.2 [0.2] vs 0.14 [0.2] kg; P < .0001) and similar in schizophrenia and bipolar disorder. Mean changes differed for asenapine versus placebo in triglycerides (1.8 [6.3] vs -12.2 [5.9] mg/dL; P < .01) and fasting glucose (1.9 [1.7] vs -1.6 [1.5] mg/dL; P < .05). In the olanzapine-controlled trials, weight change was significantly lower with asenapine than with olanzapine (0.9 [0.1] vs 3.1 [0.2] kg; P < .0001). Changes associated with asenapine were lower than those with olanzapine in fasting glucose (2.0 vs 3.3 mg/dL), total cholesterol (-0.4 [1.1] vs 6.2 [1.2] mg/dL; P < .0001), low-density lipoprotein cholesterol (-0.3 [1.1] vs 3.1 [1.2] mg/dL; P < .01), and triglycerides (-0.9 [5.4] vs 24.3 [5.8] mg/dL; P < .0001). Asenapine was associated with greater weight gain and glucose changes than placebo and not associated with a meaningful change in triglycerides or cholesterol levels. Asenapine was not significantly different from olanzapine in change in glucose levels and lower than olanzapine with respect to triglycerides, weight gain, and increased cholesterol.

Asenapine in bipolar I disorder: evidence and place in patient management

Asenapine is a new second-generation antipsychotic approved in September 2010 by the European Medicines Agency for the treatment of bipolar disorder. It demonstrated significant efficacy compared with placebo in acute mania or mixed episodes as monotherapy or adjunctive therapy to mood stabilizers (lithium or valproate). Early improvement was noted at day 2 and was strongly associated with response and remission at week 3. Asenapine also appeared effective in treating acute mania in older patients with bipolar disorder. Post hoc analyses of asenapine showed efficacy in treating depressive symptoms during manic or mixed episodes compared with placebo. The efficacy of asenapine in patients with acute mania appeared to remain constant during maintenance treatment. Asenapine was reasonably well tolerated, especially with regard to metabolic effects. There were minimal signs of glucose elevation or lipid changes and the risk of weight gain appeared limited. The prolactin elevation was smaller than other antipsychotic comparators. Only oral hypoesthesia occurred as a new adverse event compared with other second-generation antipsychotics. Asenapine presents several advantages over other second-generation antipsychotics, such as sublingual formulation, early efficacy and good metabolic tolerability. This tolerability profile confirms the heterogeneity of the second-generation antipsychotic class and supports the view of some authors for the need to re-evaluate the boundaries of this group.

P.2.e.019 Remission of manic and depressive symptoms with asenapine in patients with mixed episodes

Interleukin 6 (IL-6), a tumor promoting cytokine, has been largely implicated in the development of renal cell carcinoma (RCC). Hepatocyte cell adhesion molecule (hepaCAM) is a novel tumor suppressor, which is lost or down-regulated in many cancer types including RCC. In the present study, we intensively investigated the connection between IL-6 and hepaCAM in RCC. Our analysis of RCC tissues, adjacent tissues and paired serum samples from RCC patients revealed that IL-6 was elevated in patient serum and RCC tissue, whereas hepaCAM was completely lost or significantly down-regulated. Furthermore, we observed an association between IL-6 increase and hepaCAM decrease in RCC tissue samples. In the section of cytological researches, we found in RCC cell lines that IL-6 was a direct upstream regulator of hepaCAM, and that hepaCAM down-regulation was involved in IL-6-driven cell proliferation. We also demonstrated that IL-6-mediated promoter hypermethylation largely accounted for the hepaCAM loss in RCC, and it was STAT3-dependent. Additionally, our data showed that DNMT1 up-regulation induced by IL-6/STAT3 signaling was indispensable for IL-6-mediated hepaCAM loss in RCC cell lines ACHN and 769-P, while DNMT3b up-regulation was crucial for hepaCAM loss in A498. Our findings provide a novel signal pathway regulating cell proliferation, potentially representing a therapeutic target for RCC.

C.06.02 Can our patients do better? The relationship between motivational deficits and functional outcomes

Asenapine is approved in the United States for acute treatment of manic or mixed episodes of bipolar I disorder with or without psychotic features. We report the results of long-term treatment with asenapine in patients with bipolar I disorder.Patients completing either of two 3-week efficacy trials and a subsequent 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 phase maintained their preestablished treatment; those originally randomized to placebo received flexible-dose asenapine (placebo/asenapine). Safety and tolerability endpoints included adverse events (AEs), extrapyramidal symptoms, laboratory values, and anthropometric measures. Efficacy, a secondary assessment, was measured as change in Young Mania Rating Scale (YMRS) total score from 3-week trial baseline to week 52 with asenapine or olanzapine; the placebo/asenapine group was assessed for safety only.Incidence of treatment-emergent AEs was 71.9%, 86.1%, and 79.4% with placebo/asenapine, asenapine, and olanzapine, respectively. The most frequent treatment-emergent AEs were headache and somnolence with placebo/asenapine; insomnia, sedation, and depression with asenapine; and weight gain, somnolence, and sedation with olanzapine. Among observed cases, mean ± SD changes in YMRS total score at week 52 were − 28.6 ± 8.1 and − 28.2 ± 6.8 for asenapine and olanzapine, respectively.The study did not have a long-term placebo group.In this 52-week extension in patients with bipolar mania, asenapine was well tolerated and long-term maintenance of efficacy was supported.

P-214 - Incidence, onset and duration of treatment-emergent somnolence with asenapine in patients with schizophrenia or bipolar disorder

Introduction & objective Assess the incidence and time-course of somnolence in placebo- and active-controlled asenapine schizophrenia and bipolar I disorder (BD) trials. Methods 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. Results 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. Conclusions 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.

Long-Term Assessment of Asenapine vs. Olanzapine in Patients with Schizophrenia or Schizoaffective Disorder

INTRODUCTION We conducted a double-blind 1-year trial of asenapine in patients with schizophrenia or schizoaffective disorder. METHODS Patients were randomized to asenapine (5 or 10 mg BID; n=913) or olanzapine (10-20 mg QD; n=312), and monitored regularly. RESULTS Trial completion rates were 38% with asenapine, 57% with olanzapine; main reasons for discontinuation were withdrawal of consent (22%, 16%) and insufficient response (25%, 14%); fewer discontinuations were due to adverse events (6%, 7%). Mean weight gain was 0.9 kg with asenapine, 4.2 kg with olanzapine. Extrapyramidal symptoms reported as adverse events were more common with asenapine. Mean reductions in PANSS total score with asenapine and olanzapine were -21.0 and -27.5 ( P<0.0001); the exclusion of patients who had previous poor experience with olanzapine may have biased the results in favor of olanzapine. Scores on the subjective well-being on neuroleptics scale and functionality measures were similar between groups. CONCLUSION Asenapine was well tolerated over 1 year of treatment, causing less weight gain than olanzapine but more frequent extrapyramidal symptoms. PANSS total score improved with both agents; the improvement was greater with olanzapine than with asenapine using last observations carried forward but not in an observed-case analysis.

Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials

BackgroundAsenapine demonstrated superiority over placebo for mania in bipolar I disorder patients experiencing acute current manic or mixed episodes in 2 randomized, placebo-and olanzapine-controlled trials. We report the results of exploratory pooled post hoc analyses from these trials evaluating asenapine's effects on depressive symptoms in patients from these trials with significant baseline depressive symptoms.MethodsIn the original trials (A7501004 [NCT00159744], A7501005 [NCT00159796]), 977 patients were randomized to flexible-dose sublingual asenapine (10 mg twice daily on day 1; 5 or 10 mg twice daily thereafter), placebo, or oral olanzapine 5-20 mg once daily for 3 weeks. Three populations were defined using baseline depressive symptoms: (1) Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥20 (n = 132); (2) Clinical Global Impression for Bipolar Disorder-Depression (CGI-BP-D) scale severity score ≥4 (n = 170); (3) diagnosis of mixed episodes (n = 302) by investigative site screening. For each population, asenapine and olanzapine were independently compared with placebo using least squares mean change from baseline on depressive symptom measures.ResultsDecreases in MADRS total score were statistically greater with asenapine versus placebo at days 7 and 21 in all populations; differences between olanzapine and placebo were not significant. Decreases in CGI-BP-D score were significantly greater with asenapine versus placebo at day 7 in all categories and day 21 in population 1; CGI-BP-D score reductions were significantly greater with olanzapine versus placebo at day 21 in population 1 and day 7 in populations 2 and 3.ConclusionsThese post hoc analyses show that asenapine reduced depressive symptoms in bipolar I disorder patients experiencing acute manic or mixed episodes with clinically relevant depressive symptoms at baseline; olanzapine results appeared to be less consistent. Controlled studies of asenapine in patients with acute bipolar depression are necessary to confirm the generalizability of these findings.

Asenapine for long-term treatment of bipolar disorder: A double-blind 40-week extension study

Background Asenapine is approved in the United States for acute treatment of manic or mixed episodes of bipolar I disorder with or without psychotic features. We report the results of long-term treatment with asenapine in patients with bipolar I disorder. Methods Patients completing either of two 3-week efficacy trials and a subsequent 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 phase maintained their preestablished treatment; those originally randomized to placebo received flexible-dose asenapine (placebo/asenapine). Safety and tolerability endpoints included adverse events (AEs), extrapyramidal symptoms, laboratory values, and anthropometric measures. Efficacy, a secondary assessment, was measured as change in Young Mania Rating Scale (YMRS) total score from 3-week trial baseline to week 52 with asenapine or olanzapine; the placebo/asenapine group was assessed for safety only. Results Incidence of treatment-emergent AEs was 71.9%, 86.1%, and 79.4% with placebo/asenapine, asenapine, and olanzapine, respectively. The most frequent treatment-emergent AEs were headache and somnolence with placebo/asenapine; insomnia, sedation, and depression with asenapine; and weight gain, somnolence, and sedation with olanzapine. Among observed cases, mean ± SD changes in YMRS total score at week 52 were − 28.6 ± 8.1 and − 28.2 ± 6.8 for asenapine and olanzapine, respectively. Limitations The study did not have a long-term placebo group. Conclusions In this 52-week extension in patients with bipolar mania, asenapine was well tolerated and long-term maintenance of efficacy was supported.

Long-Term Assessment of Asenapine vs. Olanzapine in Patients with Schizophrenia or Schizoaffective Disorder

We conducted a double-blind 1-year trial of asenapine in patients with schizophrenia or schizoaffective disorder. Patients were randomized to asenapine (5 or 10 mg BID; n=913) or olanzapine (10-20 mg QD; n=312), and monitored regularly. Trial completion rates were 38% with asenapine, 57% with olanzapine; main reasons for discontinuation were withdrawal of consent (22%, 16%) and insufficient response (25%, 14%); fewer discontinuations were due to adverse events (6%, 7%). Mean weight gain was 0.9 kg with asenapine, 4.2 kg with olanzapine. Extrapyramidal symptoms reported as adverse events were more common with asenapine. Mean reductions in PANSS total score with asenapine and olanzapine were -21.0 and -27.5 ( P<0.0001); the exclusion of patients who had previous poor experience with olanzapine may have biased the results in favor of olanzapine. Scores on the subjective well-being on neuroleptics scale and functionality measures were similar between groups. Asenapine was well tolerated over 1 year of treatment, causing less weight gain than olanzapine but more frequent extrapyramidal symptoms. PANSS total score improved with both agents; the improvement was greater with olanzapine than with asenapine using last observations carried forward but not in an observed-case analysis.

P01-69 - Long-term asenapine treatment for bipolar disorder: a double-blind 40-week extension study

ObjectivesAsenapine 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.MethodsPatients 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.ResultsIncidence 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.ConclusionsIn this 52-week study, asenapine was well tolerated and long-term maintenance of efficacy was supported in patients initially presenting with bipolar mania.

Modeling and Simulation of the Time Course of Asenapine Exposure Response and Dropout Patterns in Acute Schizophrenia

Modeling and simulation were utilized to characterize the efficacy dose response of sublingual asenapine in patients with schizophrenia and to understand the outcomes of six placebo-controlled trials in which placebo responses and dropout rates varied. The time course of total Positive and Negative Syndrome Scale (PANSS) scores was characterized for placebo and asenapine treatments in a pharmacokinetic-pharmacodynamic model in which the asenapine effect was described by an E(max) model, increasing linearly over the 6-week study period. A logistic regression model described the time course of dropouts, with previous PANSS value being the most important predictor. The last observation carried forward (LOCF) time courses were well described in simulations from the combined PANSS + dropout model. The observed trial outcomes were successfully predicted for all the placebo arms and the majority of the treatment arms. Although simulations indicated that the post hoc probability of success of the performed trials was low to moderate, these analyses demonstrated that 5 and 10 mg twice-daily (b.i.d.) doses of asenapine have similar efficacy.

P.2.e.024 Double-blind extension studies of asenapine in patients with bipolar mania

P.2.e.024 Double-blind extension studies of asenapine in patients with bipolar mania

35 – Long-term safety of asenapine in patients with schizophrenia

Background: Asenapine is a novel psychopharmacologic agent under development for treatment of schizophrenia and bipolar mania. This trial focused on the long-term safety of asenapine in patients with schizophrenia. Methods: In this double-blind, non-US, 1-year-long Phase III trial, patients were randomly assigned (3:1) to asenapine, 10–20 mg, or olanzapine, 20–40 mg, daily. Safety assessments included adverse events (AEs), body weight, and laboratory examinations. Other assessments included the Subjective Well-Being on Neuroleptics (SWN) scale, Short Form (SF-12) health survey, and PANSS (using mixed model for repeated measures). Results: Among 1219 treated patients, the final dose was 10 mg/day for 53% and 59% of patients in the asenapine and olanzapine groups, respectively. Drug-related AEs (mostly mild-to-moderate) occurred in 60% and 61% of patients on asenapine and olanzapine, respectively; withdrawals due to serious AEs were similar (6.3% and 6.8%). Incidence of EPS was 18% and 8%; mean weight gain was 1.6 kg and 5.6 kg; significant weight gain (≥7%) was 14.7% with asenapine and 36.1% with olanzapine. In both groups, the incidence of QTcFN500 ms or prolongation N60 ms was 0% and 0.3%. Both groups showed small mean declines in prolactin levels. Mean changes in fasting glucose, cholesterol, and triglycerides were small in both groups. Similar responses on SWN and SF-12 assessments were observed. The difference in PANSS total score between groups was 0.5 at week 6 and 4.2 points at week 52. Conclusions: Long-term treatment (1 year) with asenapine was well tolerated in patients with schizophrenia.

Efficacy and safety of asenapine in patients with acute exacerbation of schizophrenia

Efficacy and safety of asenapine in patients with acute exacerbation of schizophrenia

Long-term sertraline treatment of obsessive compulsive disorder: a 52-week double-blind comparative study versus placebo

Asenapine is approved in the United States for acute treatment of manic or mixed episodes of bipolar I disorder with or without psychotic features. We report the results of long-term treatment with asenapine in patients with bipolar I disorder.Patients completing either of two 3-week efficacy trials and a subsequent 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 phase maintained their preestablished treatment; those originally randomized to placebo received flexible-dose asenapine (placebo/asenapine). Safety and tolerability endpoints included adverse events (AEs), extrapyramidal symptoms, laboratory values, and anthropometric measures. Efficacy, a secondary assessment, was measured as change in Young Mania Rating Scale (YMRS) total score from 3-week trial baseline to week 52 with asenapine or olanzapine; the placebo/asenapine group was assessed for safety only.Incidence of treatment-emergent AEs was 71.9%, 86.1%, and 79.4% with placebo/asenapine, asenapine, and olanzapine, respectively. The most frequent treatment-emergent AEs were headache and somnolence with placebo/asenapine; insomnia, sedation, and depression with asenapine; and weight gain, somnolence, and sedation with olanzapine. Among observed cases, mean ± SD changes in YMRS total score at week 52 were − 28.6 ± 8.1 and − 28.2 ± 6.8 for asenapine and olanzapine, respectively.The study did not have a long-term placebo group.In this 52-week extension in patients with bipolar mania, asenapine was well tolerated and long-term maintenance of efficacy was supported.