Pharmacology and efficacy of asenapine for manic and mixed states in adults with bipolar disorder

Abstract

Asenapine sublingual is a novel atypical antipsychotic approved in August 2009 for the acute treatment of schizophrenia, as well as for manic or mixed episodes as part of adult bipolar I disorder. Asenapine’s in vitro profile is similar to other atypical antipsychotic agents insofar as there is higher affinity for serotonin 5-HT_2A versus dopamine D₂ receptors. Asenapine exhibits a unique effect on monoamine, histamine and muscarinic receptor affinities, as well as effects on NMDA and AMPA receptors. This pharmacodynamic signature may mediate its symptom relief in positive, negative and mood symptoms, as well as conferring upon this agent an improved tolerability and safety profile when compared with some atypical agents. Asenapine has a relatively low propensity for changes in metabolic parameters, body composition, sedation/somnolence and extrapyramidal side effects, and is not associated with prolactin elevation or clinically significant electrocardiographic changes. Asenapine is available only in sublingual formulation, which has advantages (e.g., patient acceptance, compliance, difficulty swallowing) as well as disadvantages (i.e., patients are encouraged not to eat or drink within 10 min of administration). Its efficacy in mania is unequivocally established as is the sustaining of its acute antimanic effect. Its antidepressant and recurrence prevention effects in bipolar disorder are under investigation, as is its possible role in major depressive disorder.

Keywords::

• asenapine
• bipolar disorder
• manic
• mixed state
• pharmacology

Financial & competing interests disclosure

Roger S McIntyre has received research or grants from from Stanley Medical Research Institute and the National Alliance for Research on Schizophrenia and Depression (NARSAD), as well as research grants from Eli Lilly, Janssen-Ortho, Shire and Astra-Zeneca. He serves on the advisory boards of Astra Zeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen-Ortho, Solvay/Wyeth, Eli Lilly, Organon, Lundbeck, Biovail, Pfizer, Shire, Merck and Schering-Plough; and is a member of the speakers bureaus of Janssen-Ortho, Astra-Zeneca, Eli Lilly, Lundbeck, Biovail and Wyeth. Roger S McIntyre has undertaken CME activities for Astra Zeneca, Bristol-Myers Squibb, France Foundation, I3CME, Solvay/Wyeth, Physicians’ Postgraduate Press, CME Outfitters, Optum Health, Merck, Schering-Plough and Eli Lilly, and received travel funds from Bristol-Myers Squibb. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.