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(®) 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 α(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 α2. 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 one-third of patients experiencing >30% improvement in total PANSS score which translates in a number needed to treat (NNT) of 9.