The second generation atypical
antipsychotic,
asenapine (
Saphris), was approved by the US FDA (August 2009) for the acute treatment of manic or mixed episodes with or without psychotic features associated with bipolar I disorder in adults as well as the acute treatment of
schizophrenia.
Asenapine exhibits a high affinity for and antagonism at several serotonergic (5-HT(2A-C), 5HT(5A), 5HT(6), 5HT(7)), dopaminergic (D(2), D(3)), alpha-
adrenergic (α(1) and α(2)), and histaminergic (H1, H2) receptor subtypes.
Asenapine is the first atypical
antipsychotic formulated as a fast-dissolving, rapidly absorbed sublingual
tablet.
Asenapine was evaluated in adults with bipolar I
disorder, manic or mixed episodes with or without psychotic features. Two identically designed 3-week registration trials confirmed the efficacy of
asenapine relative to placebo in studies that included
olanzapine as an active control. The placebo-subtracted rate of EPS (excluding
akathisia) is 5% whereas the placebo-subtracted rate of
akathisia was 2%. The placebo-subtracted rate of clinically significant
weight gain (≥7%) with
asenapine was approximately 5% during the 3-week acute
mania trials. A 9- extension trial indicated that 19% of
asenapine patients will experience clinically significant
weight gain. Clinically significant metabolic abnormalities were not observed during the acute and/or extension trials.
Asenapine can be associated with
somnolence (
asenapine 24%, placebo 6%) and does not appear to be associated with clinically significant changes in vital signs, laboratory parameters, or electrocardiographic changes.
Bipolar depression and recurrence prevention studies are required to fully characterize this novel agent's position in the treatment of
bipolar disorder.