Asenapine: a clinical review of a second-generation antipsychotic

Background: Schizophrenia and bipolar disorder are both prevalent types of psychiatric illness in the United States. As second-generation antipsychotics have become a more viable first-line treatment option, their use has been associated with a new era of adverse events (AEs), most notably metabolic and cardiovascular concerns. Although treatment options for schizophrenia and bipolar disorder have arguably improved, there continues to be a need for medications that achieve and maintain desired efficacy with minimal AEs.

Objectives: This article serves as a comprehensive review of the pharmacologic profile of the second-generation antipsychotic asenapine, as well as a review of its efficacy and safety profiles based on the findings from clinical trials in schizophrenia and bipolar disorder.

Methods: Searches of Ovid MEDLINE, EMBASE, and IDIS were conducted (January 1996 to November 2011) to identify clinical studies and other primary literature sources with the following search terms: asenapine, bipolar disorder, antipsychotic, psychosis, dopamine, and schizophrenia. Only studies of asenapine and placebo and/or active-comparator arms were included.

Results: The literature search yielded 67 unique articles, including review articles, which were excluded. The efficacy of asenapine was reported in 3 clinical studies in patients with schizophrenia, 1 each in acute and long-term settings, measured as significant changes in Positive and Negative Syndrome Scale scores over 6 and 52 weeks. Asenapine also had reported efficacy in the prevention of relapse in schizophrenia during a 26-week extension study. In addition, efficacy of asenapine was reported in 2 studies in acute mania as well as extension phases of both 9 and 40 weeks, as determined by significant changes in Young Mania Rating Scale scores. The most commonly reported AEs in these studies were somnolence (13%-24%), extrapyramidal symptoms (EPS) (7%-12%), and dizziness (11%).

Conclusions: The findings from multiple studies have suggested that asenapine is efficacious in the acute treatment of schizophrenia. Asenapine has reported long-term efficacy for this indication and the potential to reduce the incidence of relapse. Asenapine efficacy was also reported in the treatment of acute manic or mixed states associated with bipolar I disorder. Asenapine had an acceptable safety profile across the different disease states studied, although it was not devoid of metabolic and EPS-related AEs.