Transdermal Asenapine in Schizophrenia: A Systematic Review

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.

A systematic review of transdermal asenapine was done utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model.

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 α₁-acid glycoprotein. It has a unique receptor profile in which it functions as an antagonist at multiple receptors with affinity that is higher than D₂ (K_i = 1.3) including D₃, D₄, 5HT_2A, 5HT_2C, 5HT_2B, 5HT₇, 5HT₆, H₁, 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.