Asenapine

Abstract

Asenapine is a novel psychopharmacological agent that binds with high affinity and specificity to numerous dopamine, serotonin, noradrenaline (norepinephrine) and histamine receptor subtypes. It is being developed for the treatment of schizophrenia and bipolar mania. In two randomized, controlled trials of asenapine monotherapy and in one randomized, controlled trial of adjunctive asenapine therapy in adult patients with bipolar I disorder, sublingual asenapine produced significantly greater reductions from baseline than placebo in clinician-assessed Young Mania Rating Scale (YMRS) total score at 3 weeks. In two randomized, controlled trials in adult patients with acute schizophrenia, treatment with asenapine reduced from baseline the clinician-assessed Positive and Negative Syndrome Scale (PANSS) total score to a significantly greater extent than placebo at 6 weeks. In schizophrenic patients with predominant, persistent, negative symptoms, asenapine at 26 weeks reduced the Negative Symptom Assessment (NSA-16) total score from baseline to an extent similar to that observed with olanzapine. Sublingual asenapine was generally well tolerated in clinical trials, with most treatment-emergent adverse events being of mild to moderate severity. Incidence rates of clinically significant weight gain, extrapyramidal symptoms, hyperprolactinaemia and alterations in glucose or lipid metabolism were generally low.

Asenapine for schizophrenia and bipolar disorder: a review of the efficacy and safety profile for this newly approved sublingually absorbed second-generation antipsychotic

“…Of these, only one was a clinical trial report (6), the remainder included a post hoc evaluation of dropouts in six placebo-controlled short-term trials (7), a paper describing clinical trial design and rationale for the treatment of negative symptoms (8), a positron emission tomography (PET) study in healthy subjects (9), 31 papers describing preclinical laboratory and animal experiments and 12 reviews of which only one focused exclusively on asenapine (10). Query of http://www.fda.gov resulted in the acquisition of two principal documents, a briefing book for the FDA Psychopharmacologic Drugs Advisory Committee prepared by FDA staff (5) and a briefing document prepared by Schering-Plough Corporation (11).…”

Asenapine improves phencyclidine-induced object recognition deficits in the rat: evidence for engagement of a dopamine D1 receptor mechanism

“…Partial agonist activity at 5-HT 1A receptors was confirmed by the blockade of inhibitory effect of asenapine on neuronal firing in the dorsal raphe nucleus and hippocampus by the 5-HT 1A receptor antagonist WAY100635 (Ghanbari et al 2009). Studies in behavioural animal models have shown the antipsychotic and procognitive effects of asenapine Marston et al 2009;Frånberg et al 2008), which have now been clinically validated in the treatment of acute schizophrenia (Kane et al 2010;Potkin et al 2007;Weber and McCormack 2009). Although there are some preliminary data to suggest that asenapine improves cognitive deficits in schizophrenia patients (Fleming et al 2007), this requires further validation.…”

Assessment of Pharmacotherapy for Negative Symptoms of Schizophrenia

“…A recent review cited data showing a benefit of asenapine on persistent, prominent negative symptoms using the NSA-16 as a detailed measure of negative symptoms [17].…”