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Role of sublingual asenapine in treatment of schizophrenia.

Citrome L - Neuropsychiatr Dis Treat (2011)

Bottom Line: Asenapine tablets are a new option for the treatment of schizophrenia.Sublingual administration is essential because bioavailability if ingested is less than 2%.Prolactin elevation can occur, but at a rate lower than that observed for haloperidol or risperidone.

View Article: PubMed Central - PubMed

Affiliation: New York University School of Medicine, Department of Psychiatry, New York, NY, USA.

ABSTRACT
Asenapine tablets are a new option for the treatment of schizophrenia. Sublingual administration is essential because bioavailability if ingested is less than 2%. Efficacy is supported by acute and long-term randomized controlled studies conducted by the manufacturer, with asenapine 5 mg twice daily evidencing superiority over placebo in six-week studies of acute schizophrenia, and flexibly-dosed asenapine (modal dose 10 mg twice daily) superior to placebo in a 26-week maintenance of response study. Tolerability advantages over some second-generation antipsychotics, such as olanzapine, include a relatively favorable weight and metabolic profile, as demonstrated in a 52-week randomized, head-to-head, double-blind clinical trial. Although dose-related extrapyramidal symptoms and akathisia can be present, the frequency of these effects is lower than that for haloperidol and risperidone. Somnolence may also occur, and appears to be somewhat dose-dependent when examining rates of this among patients receiving asenapine for schizophrenia and bipolar disorder. Prolactin elevation can occur, but at a rate lower than that observed for haloperidol or risperidone. Unique to asenapine is the possibility of oral hypoesthesia, occurring in about 5% of participants in the clinical trials. Obstacles to the use of asenapine are the recommendations for twice-daily dosing and the need to avoid food or liquids for 10 minutes after administration, although the bioavailability is only minimally reduced if food or liquids are avoided for only two minutes.

No MeSH data available.


Related in: MedlinePlus

Number needed to treat.35
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Related In: Results  -  Collection


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f1-ndt-7-325: Number needed to treat.35

Mentions: In one of the positive trials, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily, asenapine at 10 mg twice daily (after one day at 5 mg twice daily), placebo, or an active control for assay sensitivity, ie, haloperidol at 4 mg twice daily.3 The study was international in scope and took place in 2005–2006. Patients were required to be hospitalized during the first two weeks of the study. The primary efficacy endpoint was change from baseline in the total score on the Positive and Negative Syndrome Scale (PANSS). There were two prespecified methodological approaches to assess efficacy, ie, analysis of covariance using last observation carried forward (LOCF) as the primary analysis and a mixed model for repeated measures (MMRM) as the secondary analysis. Discontinuation rates were 37.6%, 33.3%, 42.0%, and 43.4% for asenapine 5 mg twice daily, asenapine 10 mg twice daily, haloperidol, and placebo groups, respectively. The discontinuation rates due to insufficient therapeutic response were 12.8%, 16.2%, 8.9%, and 25.4%, respectively, yielding a number needed to treat (number needed to treat [NNT] = 35, see Figure 1) versus placebo to avoid discontinuation because of an insufficient therapeutic response of 8, 11, and 7 for asenapine 5 mg twice daily, asenapine 10 mg twice daily, and haloperidol, respectively. On both LOCF and MMRM analyses of change in PANSS total score, asenapine 5 mg twice daily and haloperidol were both superior to placebo, with statistically significant differences seen from day 21 onwards. However, asenapine 10 mg twice daily showed no advantage over placebo at any time point on the LOCF analysis and an advantage only at day 42 on the MMRM analysis, an effect that the authors suggest may have been due in part to the high placebo response evident in this trial. The secondary outcomes roughly mirrored the primary outcome. On the PANSS positive subscale score, asenapine 5 mg twice daily and haloperidol were superior to placebo from day 21 onwards; asenapine 10 mg twice daily showed an advantage at day 42 and study endpoint. On the LOCF analysis of change in the PANSS negative subscale, none of the treatments was superior to placebo. However, using MMRM, asenapine 5 mg twice daily demonstrated an advantage at days 35 and 42. On both the LOCF and MMRM analyses of change in the PANSS general psychopathology subscale score, asenapine 5 mg twice daily was superior to placebo from day 21 onwards, in contrast with haloperidol, which showed an advantage at day 21 only, and with asenapine 10 mg twice daily, which showed no advantage at any time point. PANSS Marder factor scores were also determined, and on both the LOCF and MMRM analyses, all active treatment regimens were superior to placebo on the positive factor, but none showed an advantage on the negative factor. On both analyses of the hostility/excitement factor, only haloperidol was superior to placebo. Asenapine 5 mg twice daily was the only intervention that demonstrated superiority to placebo on the anxiety/depression factor (by MMRM) and the disorganized thought factor (by LOCF and MMRM). Categorical response, defined as a minimum decrease of 30% on the PANSS total score or a Clinical Global Impression-Improvement (CGI-I) score of 1 (ie, very much improved) or 2 (much improved), were for PANSS 55%, 49%, 43%, and 33%, for asenapine 5 mg twice daily, asenapine 10 mg twice daily, haloperidol, or placebo, respectively, yielding a NNT = 5, 7, and 10 versus placebo for asenapine 5 mg twice daily, asenapine 10 mg twice daily, and haloperidol, respectively. Similarly, CGI-I responders at endpoint were 48%, 44%, 44%, and 34%, for asenapine 5 mg twice daily, asenapine 10 mg twice daily, haloperidol or placebo, respectively, yielding a NNT = 8, 10, and 10 versus placebo for asenapine 5 mg twice daily, asenapine 10 mg twice daily, and haloperidol, respectively. Using change in CGI-I change as the outcome of interest, asenapine 5 mg twice daily and haloperidol were both significantly superior to placebo from day 21 onwards (by LOCF and MMRM).


Role of sublingual asenapine in treatment of schizophrenia.

Citrome L - Neuropsychiatr Dis Treat (2011)

Number needed to treat.35
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104691&req=5

f1-ndt-7-325: Number needed to treat.35
Mentions: In one of the positive trials, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily, asenapine at 10 mg twice daily (after one day at 5 mg twice daily), placebo, or an active control for assay sensitivity, ie, haloperidol at 4 mg twice daily.3 The study was international in scope and took place in 2005–2006. Patients were required to be hospitalized during the first two weeks of the study. The primary efficacy endpoint was change from baseline in the total score on the Positive and Negative Syndrome Scale (PANSS). There were two prespecified methodological approaches to assess efficacy, ie, analysis of covariance using last observation carried forward (LOCF) as the primary analysis and a mixed model for repeated measures (MMRM) as the secondary analysis. Discontinuation rates were 37.6%, 33.3%, 42.0%, and 43.4% for asenapine 5 mg twice daily, asenapine 10 mg twice daily, haloperidol, and placebo groups, respectively. The discontinuation rates due to insufficient therapeutic response were 12.8%, 16.2%, 8.9%, and 25.4%, respectively, yielding a number needed to treat (number needed to treat [NNT] = 35, see Figure 1) versus placebo to avoid discontinuation because of an insufficient therapeutic response of 8, 11, and 7 for asenapine 5 mg twice daily, asenapine 10 mg twice daily, and haloperidol, respectively. On both LOCF and MMRM analyses of change in PANSS total score, asenapine 5 mg twice daily and haloperidol were both superior to placebo, with statistically significant differences seen from day 21 onwards. However, asenapine 10 mg twice daily showed no advantage over placebo at any time point on the LOCF analysis and an advantage only at day 42 on the MMRM analysis, an effect that the authors suggest may have been due in part to the high placebo response evident in this trial. The secondary outcomes roughly mirrored the primary outcome. On the PANSS positive subscale score, asenapine 5 mg twice daily and haloperidol were superior to placebo from day 21 onwards; asenapine 10 mg twice daily showed an advantage at day 42 and study endpoint. On the LOCF analysis of change in the PANSS negative subscale, none of the treatments was superior to placebo. However, using MMRM, asenapine 5 mg twice daily demonstrated an advantage at days 35 and 42. On both the LOCF and MMRM analyses of change in the PANSS general psychopathology subscale score, asenapine 5 mg twice daily was superior to placebo from day 21 onwards, in contrast with haloperidol, which showed an advantage at day 21 only, and with asenapine 10 mg twice daily, which showed no advantage at any time point. PANSS Marder factor scores were also determined, and on both the LOCF and MMRM analyses, all active treatment regimens were superior to placebo on the positive factor, but none showed an advantage on the negative factor. On both analyses of the hostility/excitement factor, only haloperidol was superior to placebo. Asenapine 5 mg twice daily was the only intervention that demonstrated superiority to placebo on the anxiety/depression factor (by MMRM) and the disorganized thought factor (by LOCF and MMRM). Categorical response, defined as a minimum decrease of 30% on the PANSS total score or a Clinical Global Impression-Improvement (CGI-I) score of 1 (ie, very much improved) or 2 (much improved), were for PANSS 55%, 49%, 43%, and 33%, for asenapine 5 mg twice daily, asenapine 10 mg twice daily, haloperidol, or placebo, respectively, yielding a NNT = 5, 7, and 10 versus placebo for asenapine 5 mg twice daily, asenapine 10 mg twice daily, and haloperidol, respectively. Similarly, CGI-I responders at endpoint were 48%, 44%, 44%, and 34%, for asenapine 5 mg twice daily, asenapine 10 mg twice daily, haloperidol or placebo, respectively, yielding a NNT = 8, 10, and 10 versus placebo for asenapine 5 mg twice daily, asenapine 10 mg twice daily, and haloperidol, respectively. Using change in CGI-I change as the outcome of interest, asenapine 5 mg twice daily and haloperidol were both significantly superior to placebo from day 21 onwards (by LOCF and MMRM).

Bottom Line: Asenapine tablets are a new option for the treatment of schizophrenia.Sublingual administration is essential because bioavailability if ingested is less than 2%.Prolactin elevation can occur, but at a rate lower than that observed for haloperidol or risperidone.

View Article: PubMed Central - PubMed

Affiliation: New York University School of Medicine, Department of Psychiatry, New York, NY, USA.

ABSTRACT
Asenapine tablets are a new option for the treatment of schizophrenia. Sublingual administration is essential because bioavailability if ingested is less than 2%. Efficacy is supported by acute and long-term randomized controlled studies conducted by the manufacturer, with asenapine 5 mg twice daily evidencing superiority over placebo in six-week studies of acute schizophrenia, and flexibly-dosed asenapine (modal dose 10 mg twice daily) superior to placebo in a 26-week maintenance of response study. Tolerability advantages over some second-generation antipsychotics, such as olanzapine, include a relatively favorable weight and metabolic profile, as demonstrated in a 52-week randomized, head-to-head, double-blind clinical trial. Although dose-related extrapyramidal symptoms and akathisia can be present, the frequency of these effects is lower than that for haloperidol and risperidone. Somnolence may also occur, and appears to be somewhat dose-dependent when examining rates of this among patients receiving asenapine for schizophrenia and bipolar disorder. Prolactin elevation can occur, but at a rate lower than that observed for haloperidol or risperidone. Unique to asenapine is the possibility of oral hypoesthesia, occurring in about 5% of participants in the clinical trials. Obstacles to the use of asenapine are the recommendations for twice-daily dosing and the need to avoid food or liquids for 10 minutes after administration, although the bioavailability is only minimally reduced if food or liquids are avoided for only two minutes.

No MeSH data available.


Related in: MedlinePlus