Transdermal Asenapine in Schizophrenia: A Systematic Review

Background: Asenapine is a novel antipsychotic that has demonstrated efficacy in controlling psychosis in schizophrenia and mania in bipolar illness. It must be administered as a sublingual formulation because it is nearly completely metabolized in the first pass through the liver. Recently, a transdermal formulation of asenapine has been approved for schizophrenia by the Food and Drug Administration. Methods: A systematic review of transdermal asenapine was done utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model. Discussion: There are several formulations of transdermal asenapine but only Secuado (R) has been approved for clinical use. Total bioavailability is 35%. Peak plasma concentration (Cmax) is 4 ng/mL and occurs within 1 hr (Tmax); elimination half-life (t(1/2)) is 24 hrs (range 13.4 to 39.2 h). Asenapine is highly bound (95%) to albumin and alpha(1)-acid glycoprotein. It has a unique receptor profile in which it functions as an antagonist at multiple receptors with affinity that is higher than D-2 (K-i = 1.3) including D-3, D-4, 5HT(2A), 5HT(2C), 5HT(2B), 5HT(7), 5HT(6), H-1, and alpha(2). This profile suggests that asenapine may be of particular value off label for bipolar depression, anxiety, and aggression. Transdermal asenapine was only tested in one randomized, placebo-controlled study of acute psychosis in schizophrenia. It was superior to placebo at week 6 with nearly onethird of patients experiencing >30% improvement in total PANSS score which translates in a number needed to treat (NNT) of 9.