|Trade names||Saphris, Sycrest, Secuado, others|
|Other names||Asenapine maleate, ORG-5222|
|Drug class||Atypical antipsychotic|
|Main uses||Schizophrenia, mania in bipolar disorder|
|Side effects||Sleepiness, dizziness, weight gain, movement disorders, numbness within the mouth|
|Under the tongue|
|Bioavailability||35% (sublingual), <2% (by mouth)|
|Metabolism||hepatic (glucurinodation by UGT1A4 and oxidative metabolism by CYP1A2)|
|Elimination half-life||24 hours|
|Excretion||Kidney (50%), Faecal (40%; ~5–16% as unchanged drug in faeces)|
|Chemical and physical data|
|Molar mass||285.77 g·mol−1|
|3D model (JSmol)|
Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic used to treat schizophrenia and mania in bipolar disorder. Use in older people with dementia related psychosis may increase the risk of death. It is used under the tongue.
Common side effects include sleepiness, dizziness, weight gain, movement disorders, and numbness within the mouth. Other side effects may include stroke, neuroleptic malignant syndrome, tardive dyskinesia, diabetes, low white blood cells, seizures, and QT prolongation. How it works is not clear, but is believed to involve blocking serotonin and dopamine receptors.
Asenapine was approved for medical use in the United States in 2009 and Europe in 2010. The first generic versions were approved in 2020. In the United Kingdom it costs the NHS about £100 per month as of 2021. This amount in the United States is about 200 USD.
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:
- 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
A Cochrane 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.
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 (with the exception of ziprasidone) such as risperidone and olanzapine. Drop-out rates (in clinical trials) 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.
It is generally taken at 5 mg twice per day though may be increased up to 10 mg twice per day.
Very common (>10%):
- Weight gain
- Increased appetite
- Extrapyramidal side effects (EPS; such as dystonia, akathisia, dyskinesia, muscle rigidity, parkinsonism)
- Oral hypoaesthesia
- Increased alanine aminotransferase
- Hyperglycaemia — elevated blood glucose (sugar)
- sinus bradycardia
- Bundle branch block
- QTc interval prolongation (has a relatively low risk for causing QTc interval prolongation.)
- sinus tachycardia
- Orthostatic hypotension
- Swollen tongue
- Dysphagia (difficulty swallowing)
- Oral paraesthesia
- 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
- Blood dyscrasias such as agranulocytosis, leukopenia and neutropenia
- Accommodation disorder[clarification needed]
- Pulmonary embolism
- Allergic reaction
- Restless legs syndrome
- Oral mucosal lesions (ulcerations, blistering and inflammation)
- Salivary hypersecretion
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). 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 (3.28; 95% CI: 1.37-6.69) for causing sedation [compared to placebo-treated patients] as olanzapine (3.34; 95% CI: 2.46-4.50]) and haloperidol (2.76; 95% CI: 2.04-3.66) and a higher odds ratio (although not significantly) for sedation than aripiprazole (1.84; 95% CI: 1.05-3.05), paliperidone (1.40; 95% CI: 0.85-2.19) and amisulpride (1.42; 95% CI: 0.72 to 2.51) to name a few and is hence a mild-moderately sedating antipsychotic. 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.
For all antipsychotics, the British National Formulary recommends a gradual dose reduction when discontinuing 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 recurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.
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 < 5) 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.
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