![]() | |
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Clinical data | |
---|---|
Trade names | Saphris, Sycrest |
AHFS/ Drugs.com | Monograph |
MedlinePlus | a610015 |
License data | |
Pregnancy category |
|
Routes of administration | sublingual |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 35% (sublingual), <2% (Oral) [1] [2] [3] [4] |
Protein binding | 95% [1] [2] [3] [4] |
Metabolism | hepatic (glucurinodation by UGT1A4 and oxidative metabolism by CYP1A2) [1] [2] [3] [4] |
Elimination half-life | 24 hours [1] [2] [3] [4] |
Excretion | Renal (50%), Faecal (40%; ~5-16% as unchanged drug in faeces) [1] [2] [3] [4] |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
ChemSpider | |
UNII | |
ChEBI | |
ChEMBL | |
Chemical and physical data | |
Formula | C17H16ClNO |
Molar mass | 285.77 g/mol g·mol−1 |
3D model ( JSmol) | |
| |
| |
![]() ![]() |
Asenapine, sold under the trade names Saphris and Sycrest, is an atypical antipsychotic developed for the treatment of schizophrenia and acute mania associated with bipolar disorder.
It was chemically derived via altering the chemical structure of the tetracyclic (atypical) antidepressant, mianserin. [5]
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. [6] In Australia asenapine's approved (and also listed on the PBS) indications include the following: [7]
In the European Union and the UK asenapine is only licensed for use as a treatment for acute mania in bipolar I disorder. [3] [4]
Absorbed readily if administered sublingually, asenapine is poorly absorbed when swallowed. [8]
In a 2013 study in a comparison of 15 antipsychotic drugs in effectivity in treating schizophrenic symptoms, asenapine demonstrated low-medium effectivity. Less effective than clozapine, slightly less effective than haloperidol, quetiapine, and aripiprazole, approximately as effective as ziprasidone and chlorpromazine, and slightly more effective than lurasidone. [9] It appears to be less efficacious than other antipsychotics in the treatment of schizophrenia, [10] although its all-cause discontinuation rate is moderate. [10]A 2015 systematic review examined the effects of asenapine for people with schizophrenia:
Summary | ||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
There is some, albeit preliminary, evidence that asenapine provides an improvement in positive, negative, and depressive symptoms, whilst having few adverse effects. However, due to the low-quality and limited quantity of evidence, it remains difficult to recommend the use of asenapine for people with schizophrenia. There is need for large-scale, longer-term, better-designed and conducted randomized controlled trials investigating the clinical effects and safety of asenapine. [11] | ||||||||||||||||||||||||||||||||||||||||||||
|
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. [12] 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. [13]
Adverse effect incidence
[1]
[2]
[3]
[4]
Note: The discussion below these lists provides some more context into the frequency and severity of these adverse effects.
Very common (>10% incidence) adverse effects include:
Common (1-10% incidence) adverse effects include:
Uncommon (0.1-1% incidence) adverse effects include:
Rare (0.01-0.1% incidence) adverse effects include:
Unknown incidence adverse effects
Asenapine seems to have a relatively low weight gain liability for an atypical antipsychotic (which are notorious for their metabolic side effects) and according to a recent meta-analysis it produces
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).
[10] Its potential for elevating plasma prolactin levels seems relatively limited too according to this meta-analysis.
[10] 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.
[10] Being a second-generation (atypical) 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 (although this meta-analysis did reveal it had a relatively high EPS liability for an atypical antipsychotic drug).
[10]
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. [16] At all other targets asenapine is an antagonist. [17] As of November 2010 asenapine is also in clinical trials at UC Irvine to treat stuttering.
Receptor | Affinity (pKi) [17] | Affinity (Ki (nM)) [6] |
---|---|---|
5-HT1A | 8.6 (agonist) | 2.5 (agonist) |
5-HT1B | 8.4 | 4.0 |
5-HT2A | 10.2 | 0.06 |
5-HT2B | 9.8 | 0.16 |
5-HT2C | 10.5 | 0.03 |
5-HT5A | 8.8 | 1.6 |
5-HT6 | 9.5 | 0.25 |
5-HT7 | 9.9 | 0.13 |
α1-Adrenergic | 8.9 | 1.2 |
α2A-Adrenergic | 8.9 | 1.2 |
α2B-Adrenergic | 9.5 | 0.32 |
α2C-Adrenergic | 8.9 | 1.2 |
D1 | 8.9 | 1.4 |
D2 | 8.9 | 1.3 |
D3 | 9.4 | 0.42 |
D4 | 9.0 | 1.1 |
H1 | 9.0 | 1.0 |
H2 | 8.2 | 6.2 |
mACh | < 5 | 8,128 |
Its developed by Schering-Plough after its November 19, 2007 merger with Organon International. Though Phase III trials, began while Organon was still a part of Akzo Nobel. [18] Preliminary data indicate that it has minimal anticholinergic and cardiovascular side effects, as well as minimal weight gain. Over 3000 people have participated in clinical trials of asenapine, and the FDA approved the manufacturer's NDA in August 2009. [19]
{{
cite journal}}
: CS1 maint: unflagged free DOI (
link)
![]() | |
![]() | |
Clinical data | |
---|---|
Trade names | Saphris, Sycrest |
AHFS/ Drugs.com | Monograph |
MedlinePlus | a610015 |
License data | |
Pregnancy category |
|
Routes of administration | sublingual |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 35% (sublingual), <2% (Oral) [1] [2] [3] [4] |
Protein binding | 95% [1] [2] [3] [4] |
Metabolism | hepatic (glucurinodation by UGT1A4 and oxidative metabolism by CYP1A2) [1] [2] [3] [4] |
Elimination half-life | 24 hours [1] [2] [3] [4] |
Excretion | Renal (50%), Faecal (40%; ~5-16% as unchanged drug in faeces) [1] [2] [3] [4] |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
ChemSpider | |
UNII | |
ChEBI | |
ChEMBL | |
Chemical and physical data | |
Formula | C17H16ClNO |
Molar mass | 285.77 g/mol g·mol−1 |
3D model ( JSmol) | |
| |
| |
![]() ![]() |
Asenapine, sold under the trade names Saphris and Sycrest, is an atypical antipsychotic developed for the treatment of schizophrenia and acute mania associated with bipolar disorder.
It was chemically derived via altering the chemical structure of the tetracyclic (atypical) antidepressant, mianserin. [5]
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. [6] In Australia asenapine's approved (and also listed on the PBS) indications include the following: [7]
In the European Union and the UK asenapine is only licensed for use as a treatment for acute mania in bipolar I disorder. [3] [4]
Absorbed readily if administered sublingually, asenapine is poorly absorbed when swallowed. [8]
In a 2013 study in a comparison of 15 antipsychotic drugs in effectivity in treating schizophrenic symptoms, asenapine demonstrated low-medium effectivity. Less effective than clozapine, slightly less effective than haloperidol, quetiapine, and aripiprazole, approximately as effective as ziprasidone and chlorpromazine, and slightly more effective than lurasidone. [9] It appears to be less efficacious than other antipsychotics in the treatment of schizophrenia, [10] although its all-cause discontinuation rate is moderate. [10]A 2015 systematic review examined the effects of asenapine for people with schizophrenia:
Summary | ||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
There is some, albeit preliminary, evidence that asenapine provides an improvement in positive, negative, and depressive symptoms, whilst having few adverse effects. However, due to the low-quality and limited quantity of evidence, it remains difficult to recommend the use of asenapine for people with schizophrenia. There is need for large-scale, longer-term, better-designed and conducted randomized controlled trials investigating the clinical effects and safety of asenapine. [11] | ||||||||||||||||||||||||||||||||||||||||||||
|
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. [12] 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. [13]
Adverse effect incidence
[1]
[2]
[3]
[4]
Note: The discussion below these lists provides some more context into the frequency and severity of these adverse effects.
Very common (>10% incidence) adverse effects include:
Common (1-10% incidence) adverse effects include:
Uncommon (0.1-1% incidence) adverse effects include:
Rare (0.01-0.1% incidence) adverse effects include:
Unknown incidence adverse effects
Asenapine seems to have a relatively low weight gain liability for an atypical antipsychotic (which are notorious for their metabolic side effects) and according to a recent meta-analysis it produces
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).
[10] Its potential for elevating plasma prolactin levels seems relatively limited too according to this meta-analysis.
[10] 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.
[10] Being a second-generation (atypical) 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 (although this meta-analysis did reveal it had a relatively high EPS liability for an atypical antipsychotic drug).
[10]
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. [16] At all other targets asenapine is an antagonist. [17] As of November 2010 asenapine is also in clinical trials at UC Irvine to treat stuttering.
Receptor | Affinity (pKi) [17] | Affinity (Ki (nM)) [6] |
---|---|---|
5-HT1A | 8.6 (agonist) | 2.5 (agonist) |
5-HT1B | 8.4 | 4.0 |
5-HT2A | 10.2 | 0.06 |
5-HT2B | 9.8 | 0.16 |
5-HT2C | 10.5 | 0.03 |
5-HT5A | 8.8 | 1.6 |
5-HT6 | 9.5 | 0.25 |
5-HT7 | 9.9 | 0.13 |
α1-Adrenergic | 8.9 | 1.2 |
α2A-Adrenergic | 8.9 | 1.2 |
α2B-Adrenergic | 9.5 | 0.32 |
α2C-Adrenergic | 8.9 | 1.2 |
D1 | 8.9 | 1.4 |
D2 | 8.9 | 1.3 |
D3 | 9.4 | 0.42 |
D4 | 9.0 | 1.1 |
H1 | 9.0 | 1.0 |
H2 | 8.2 | 6.2 |
mACh | < 5 | 8,128 |
Its developed by Schering-Plough after its November 19, 2007 merger with Organon International. Though Phase III trials, began while Organon was still a part of Akzo Nobel. [18] Preliminary data indicate that it has minimal anticholinergic and cardiovascular side effects, as well as minimal weight gain. Over 3000 people have participated in clinical trials of asenapine, and the FDA approved the manufacturer's NDA in August 2009. [19]
{{
cite journal}}
: CS1 maint: unflagged free DOI (
link)