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 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 UK asenapine is only licensed for use as a treatment for acute mania in bipolar I disorder. Absorbed readily if administered sublingually, asenapine is poorly absorbed when swallowed.
Schizophrenia
In a Cochrane systemic review, senior researcher for the McPin Foundation, Ben Gray 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. Likewise, as stated, Aspenapine isn't approved for schizophrenia treatment in the UK where Cochrane organization and that reviewer is located.
Acute mania
As for its efficacy in the treatment of acute mania, a recent meta-analysis showed that it produces comparatively small improvements in manic symptoms in patients with acute mania and mixed episodes than most other antipsychotic drugs such as risperidone and olanzapine. Drop-out rates were also unusually high with asenapine. 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 effect incidence Note: The discussion below these lists provides some more context into the frequency and severity of these adverse effects. Very common adverse effects include:
Asenapine seems to have a relatively low weight gain liability for an atypical antipsychotic and according to a recent meta-analysis it produces significantly less weight gain than, paliperidone, risperidone, quetiapine, sertindole, chlorpromazine, iloperidone, clozapine, zotepine and olanzapine and approximately as much as weight gain as aripiprazole, lurasidone, amisulpride, haloperidol and ziprasidone. Its potential for elevating plasma prolactin levels seems relatively limited too according to this meta-analysis. This meta-analysis also found that asenapine has approximately the same odds ratio for causing sedation as olanzapine and haloperidol and a higher odds ratio for sedation than aripiprazole, paliperidone and amisulpride to name a few and is hence a mild-moderately sedating antipsychotic. Being a second-generation antipsychotic its liability for causing extrapyramidal side effect is comparatively low compared to first-generation antipsychotics such as haloperidol as is supported by the aforementioned meta-analysis.
Discontinuation
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time. There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.
Pharmacology
Asenapine shows high affinity for numerous receptors, including the serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5A, 5-HT6, and 5-HT7 receptors, the adrenergic α1, α2A, α2B, and α2C receptors, the dopamine D1, D2, D3, and D4 receptors, and the histamine H1 and H2 receptors. It has much lower affinity for the muscarinic acetylcholine receptors. Asenapine behaves as a partial agonist at the 5-HT1A receptors. At all other targets asenapine is an antagonist. As of November 2010 asenapine is also in clinical trials at UC Irvine to treat stuttering.
Pharmacodynamics
Based on its exceptionally high, unequaled affinity for the 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors, and very high affinity for the α2 and H1 receptors, asenapine, given normal tolerability, should theoretically demonstrate among the highest improvements in the negative symptomology of schizophrenia among all current antipsychotics, such as high cognitive improvements and positive, stable mood maintenance.
