MarketAsenapine
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Asenapine

Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder as well as the medium to long-term management of bipolar disorder.

Medical uses
Asenapine has been approved by the FDA for the acute treatment of adults with schizophrenia and acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults. In Australia asenapine's approved (and also listed on the PBS) indications include the following: • Schizophrenia • Treatment, for up to 6 months, of an episode of acute mania or mixed episodes associated with bipolar I disorder • Maintenance treatment, as monotherapy, of bipolar I disorder In the European Union and the United Kingdom, asenapine is only licensed for use as a treatment for acute mania in bipolar I disorder. A transdermal formulation of asenapine was approved in the United States in October 2019 under the brand name Secuado. Schizophrenia A Cochrane systematic review found that while Asenapine has some preliminary evidence that it improves positive, negative, and depressive symptoms, it does not have enough research to merit a certain recommendation of asenapine for the treatment of schizophrenia. Bipolar disorder For the medium-term and long-term management and control of both depressive and manic features of bipolar disorder asenapine was found to be equally effective as olanzapine, but with a substantially superior side effect profile. In acute mania, asenapine was found to be significantly superior to placebo. According to a post-hoc analysis of two 3-week clinical trials it may possess some antidepressant effects in patients with acute mania or mixed episodes. ==Adverse effects==
Adverse effects
Adverse effect incidence) • sinus tachycardia • Orthostatic hypotension • Hypotension • Swollen tongue • Dysphagia (difficulty swallowing) • Glossodynia • Oral paraesthesia Rare (0.01–0.1% incidence) adverse effects include:Neuroleptic malignant syndrome (Combination of fever, muscle stiffness, faster breathing, sweating, reduced consciousness, and sudden change in blood pressure and heart rate) • Tardive dyskinesia • Speech disturbance • RhabdomyolysisAngioedema • Blood dyscrasias such as agranulocytosis, leukopenia and neutropenia • Accommodation disorder • Pulmonary embolismGynaecomastiaGalactorrhoea Unknown incidence adverse effects • Allergic reaction • Restless legs syndrome • Oral mucosal lesions (ulcerations, blistering and inflammation) • Salivary hypersecretion • Hyperprolactinaemia Asenapine seems to have a relatively low weight gain liability for an atypical antipsychotic (which are notorious for their metabolic side effects) and a 2013 meta-analysis found significantly less weight gain (SMD [standard mean difference in weight gained in those on placebo vs. active drug]: 0.23; 95% CI: 0.07-0.39) than, paliperidone (SMD: 0.38; 95% CI: 0.27-0.48), risperidone (SMD: 0.42; 95% CI: 0.33-0.50), quetiapine (SMD: 0.43; 95% CI: 0.34-0.53), sertindole (SMD: 0.53; 95% CI: 0.38-0.68), chlorpromazine (SMD: 0.55; 95% CI: 0.34-0.76), iloperidone (SMD: 0.62; 95% CI: 0.49-0.74), clozapine (SMD: 0.65; 95% CI: 0.31-0.99), zotepine (SMD: 0.71; 95% CI: 0.47-0.96) and olanzapine (SMD: 0.74; 95% CI: 0.67-0.81) and approximately (that is, no statistically significant difference at the p=0.05 level) as much as weight gain as aripiprazole (SMD: 0.17; 95% CI: 0.05-0.28), lurasidone (SMD: 0.10; 95% CI: –0.02-0.21), amisulpride (SMD: 0.20; 95% CI: 0.05-0.35), haloperidol (SMD: 0.09; 95% CI: 0.00-0.17) and ziprasidone (SMD: 0.10; 95% CI: –0.02-0.22). The same meta-analysis suggested that asenapine had a relatively high risk of extrapyramidal symptoms compared to other atypical antipsychotics but a lower risk than first-generation or typical antipsychotics. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. It may also result in recurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped. ==Pharmacology==
Pharmacology
Pharmacodynamics Asenapine shows high affinity (pKi) for numerous receptors, including the serotonin 5-HT1A (8.6), 5-HT1B (8.4), 5-HT2A (10.2), 5-HT2B (9.8), 5-HT2C (10.5), 5-HT5A (8.8), 5-HT6 (9.5), and 5-HT7 (9.9) receptors, the adrenergic α1 (8.9), α2A (8.9), α2B (9.5), and α2C (8.9) receptors, the dopamine D1 (8.9), D2 (8.9), D3 (9.4), and D4 (9.0) receptors, and the histamine H1 (9.0) and H2 (8.2) receptors. It has much lower affinity (pKi 1A receptors. At all other targets asenapine is an antagonist. Even relative to other atypical antipsychotics, asenapine has unusually high affinity for the 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors, and very high affinity for the α2 and H1 receptors. ==Notes==
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