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Asenapine

A Review of its Use in the Management of Mania in Adults with Bipolar I Disorder

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Abstract

Asenapine is an atypical antipsychotic agent available in sublingual formulations (5 or 10mg) and indicated in the US (Saphris®) for the acute treatment, as monotherapy or adjunctive therapy, of manic and mixed episodes and in the EU (Sycrest®) for the treatment of moderate to severe manic episodes, in adult patients with bipolar I disorder.

In two large (both n = 480), well designed, 3-week trials in adult patients with bipolar I disorder, asenapine monotherapy was significantly more effective than placebo at improving mania symptoms, as assessed using the Young Mania Rating Scale total score (YMRS; primary endpoint), with significant differences between the asenapine and placebo groups occurring after 2 days of treatment. In both trials, Clinical Global Impression for Bipolar Disorder (CGI-BP) scale mania severity scores exceeded those of placebo. In one trial, response and remission rates exceeded those of placebo.

In a 9-week extension study that recruited completers from the monotherapy trials, there were no significant differences between asenapine and olanzapine groups in terms in Montgomery-Åsberg Depression Rating Scale (MADRS) scores, CGI-BP mania severity scores, YMRS response rates or YMRS remission rates during the extension phase. In the extension study, the efficacy of asenapine monotherapy appeared to be maintained over 40 weeks (total treatment duration of 52 weeks).

In a 12-week trial of asenapine as adjunctive therapy to lithium or valproate, asenapine was more effective than placebo in improving manic symptoms, based on the difference between groups in the YMRS total score at week 3 (primary endpoint).

Most adverse events associated with asenapine were of mild to moderate severity, with <7% of asenapine recipients experiencing serious adverse events (vs 7% with placebo). In a pooled analysis of the monotherapy trials, the most common adverse events (occurring in ≥5% of patients and at twice the incidence of placebo) reported during acute phase asenapine monotherapy for bipolar mania were somnolence, dizziness, extrapyramidal symptoms (EPS, other than akathisia) and increased bodyweight, which were similar in nature to those occurring during longer-term monotherapy with asenapine. EPS did not worsen in severity during longer-term asenapine monotherapy. Asenapine had minimal effects on plasma glucose, lipid and prolactin levels over both short-and longer-term treatment periods, and had little pro-arrhythmogenic potential.

Further active comparator trials and longer-term tolerability and safety data are required. In the meantime, asenapine is a further option for the management of manic and/or mixed symptoms in patients with bipolar I disorder and may be of particular value for patients who are at high risk for metabolic abnormalities.

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Authors and Affiliations

  1. Adis, a Wolters Kluwer Business, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Claudine M. Chwieduk & Lesley J. Scott

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  1. Claudine M. Chwieduk
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  2. Lesley J. Scott
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Corresponding author

Correspondence to Claudine M. Chwieduk.

Additional information

Various sections of the manuscript reviewed by: M.S. Bourin, Department of Pharmacology, University of Nantes, Nantes Cedex, France; J.R. Calabrese, Department of Psychiatry, Case Western University School of Medicine, Cleveland, Ohio, USA; S. Gentile, Department of Mental Health, Mental Health Center, Salerno, Italy; R. Ghanbari, University of Ottawa, Institute of Mental Health Research, Ottawa, Ontario, Canada; S.C. Schultz, Department of Psychiatry, University of Minnesota Medical School, Minneapolis, Minnesota, USA.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘asenapine’ was identified by searching databases since 1996 (including MEDLINE, EMBASE and in-house AdisBase), bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘asenapine’ and (‘bipolar I disorders’ and ‘mania’) or (‘bipolar mania’) or (‘bipolar’ and ‘mania’). Searches were last updated 27 January 2010.

Selection: Studies in patients who received asenapine for the management of mania associated with bipolar I disorder. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Asenapine, bipolar I disorder, mania, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

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Chwieduk, C.M., Scott, L.J. Asenapine. CNS Drugs 25, 251–267 (2011). https://doi.org/10.2165/11206700-000000000-00000

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