<p>Transdermal Asenapine in Schizophrenia: A Systematic Review</p>

Abstract

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 onethird of patients experiencing >30% improvement in total PANSS score which translates in a number needed to treat (NNT) of 9.

Pharmacokinetic Profile of the Asenapine Transdermal System (HP-3070)

“…To minimize this issue during clinical use, patients should be encouraged to rotate application sites regularly. 3 Minimal variability in irritation or discomfort was observed between patch application sites, with no irritation or discomfort reported in the presence or absence of external heat in study 1. Patch adhesion was consistently good, with more than 90% adhesion for most of the subjects and a low rate of partial detachments in each study.…”

“…Although the need for multiple types of formulations has been acknowledged in the literature 1 , 2 and a range of formulation options have been explored, 2 a transdermal delivery option for antipsychotic medications had not been available until recently. 3 …”

“…Although the need for multiple types of formulations has been acknowledged in the literature 1,2 and a range of formulation options have been explored, 2 a transdermal delivery option for antipsychotic medications had not been available until recently. 3 Asenapine, a second-generation antipsychotic, was originally commercially available only as a sublingual tablet administered twice daily with instructions that the tablet be placed under the tongue and allowed to dissolve. 4 Adverse effects related to the sublingual administration of asenapine can include oral ulcers, hypoesthesia, or dysgeusia.…”

Memantine-Derived Schiff Bases as Transdermal Prodrug Candidates

“…Considering the challenges in the current pharmacotherapy administration, the outcomes described here pave the way for new proposals aiming at future alternatives for transdermal patches that might have applications in the treatment of neuropsychiatric conditions in general, such as Schizophrenia and related disorders, − which might increase treatment adherence, with life quality improvement of patients, families, and professional caregivers.…”

Serotonin-mediated anxiety: How to recognize and treat it

“…Almost always, interventions that block multiple postsynaptic 5-HT receptors or discontinuation of the SSRI (if applicable) will alleviate the anxiety, quickly or more slowly, respectively. Sublingual asenapine, which at low doses can block 5-HT2C (Ki = 0.03 nM), 5-HT2A (Ki = 0.07 nM), 5-HT7 (Ki = 0.11 nM), 5-HT2B (Ki = 0.18 nM), and 5-HT6 (Ki = 0.25 25,26 and which will produce peak plasma levels within 10 minutes, 27 usually is quite effective. 28 A key difference: No motor system involvement What distinguishes 5-HT from the other amine transmitters as a mediator of anxiety is the lack of involvement of the motor system.…”