Divergence of dose–response with asenapine: a cluster analysis of randomized, double-blind, and placebo control study

Abstract

Background Differences in psychiatric background and dose–response to asenapine in patients with schizophrenia were examined based on efficacy and safety, using data obtained in a double-blind, placebo-controlled trial. Methods Patients with schizophrenia were classified into three clusters by a cluster analysis based on the Positive and Negative Symptom Scale (PANSS) subscores at baseline, using the data from a 6-week, double-blind, placebo-controlled trial. PANSS Marder factor scores were calculated for each cluster. The efficacy of 10 or 20 mg/day of asenapine on PANSS score was used as the primary endpoint, with the incidence of adverse events evaluated as the secondary endpoint. Results A total of 529 asenapine-treated patients were classified into 3 clusters: Cluster-P with the higher scores in positive symptoms, disorganized thoughts, and hostility/excitement, Cluster-N with higher scores in negative symptoms, and Cluster-L with overall lower scores. In Cluster-N and Cluster-L, both 10 and 20 mg/day groups showed significant improvement in PANSS scores, while only the 20 mg/day group showed a significant difference in Cluster-P. Cluster-N and Cluster-L had differences in the incidence of adverse events, but this was not seen in Cluster-P. Conclusions The efficacy and safety of asenapine 10 and 20 mg/day differed between the 3 clusters of patients. This suggests that background information regarding baseline psychiatric symptoms may affect the therapeutic response in patients with schizophrenia.

Optimal dose for the efficacy of asenapine in patients with schizophrenia: Real‐world data

“…required a dose of 20 mg/day. 9 These findings, based on short-term results, are consistent with the findings of this survey after 1 year of maintenance treatment.…”

“…A meta‐analysis of short‐term studies in patients with acute‐phase schizophrenia revealed that the effective asenapine dose for 95% of the population was 14.97 mg/day 3 . Furthermore, in a post hoc analysis of a 6‐week RCT in patients with an acute exacerbation of schizophrenia, a cluster analysis based on PANSS Marder factor scores of patients receiving asenapine suggested that some patients required a dose of 20 mg/day 9 . These findings, based on short‐term results, are consistent with the findings of this survey after 1 year of maintenance treatment.…”

Efficacy of Asenapine in Drug-resistant Psychotic Patients with Dopamine Supersensitivity Psychosis: Two Cases

“…The reported patients were all treated with asenapine 20 mg; the chlorpromazine equivalent- dose is 800 mg. Our present two patients’ symptoms were also successfully controlled with similar dose of asenapine. According to a recent sub-analysis of a clinical trial [ 26 ], a portion of patients with schizophrenia respond further to the higher dose (20 mg) of asenapine, which might also be the case for our patients. In addition, both of our patients showed EPS and hyperprolactinemia, which are common adverse effects of serotonin-dopamine antagonists.…”

Efficacy of HP-3070, A Once-Daily Asenapine Transdermal System, in the Treatment of Adults with Schizophrenia: A PANSS Five-Factor Analysis

“…The PANSS five-factor model has previously been used to analyze the results of phase 3 studies comparing the efficacy of SLA 5 mg and 10 mg BID vs placebo in patients with acute schizophrenia. 16 , 18 Dose equivalencies for SLA 5 mg and 10 mg BID are HP-3070 3.8mg/24h and 7.6mg/24h, respectively. 19 Kane et al 16 reported that after 6 weeks of treatment, both studied doses of SLA were superior to placebo on the PANSS positive symptoms domain and SLA 5 mg was superior to placebo on the anxiety/depression and disorganized thought factors, but SLA was not superior to placebo on negative symptom and hostility/excitement factors.…”