Effects of asenapine: A Synthesis of Findings from 22 Studies

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Original Abstract of the Article

Major Research Findings

Asenapine is a new psychopharmacologic agent being developed for the treatment of schizophrenia and bipolar disorder. It has a unique human receptor binding signature with strong affinity for dopaminergic, alpha-adrenergic, and, in particular, serotonergic receptors, suggesting the possibility of interactions with glutamatergic receptors. 9 investigated the distinctive regional effects of asenapine on ionotropic glutamate receptor subtypes in rat brain. They found that chronic treatment with asenapine had region-specific and dose-dependent effects on ionotropic Glu-receptor subtypes in rat forebrain. 19 studied the effects of asenapine on adrenergic and cholinergic muscarinic receptors in rat forebrain, finding that asenapine produced increases in alpha1- and alpha2-adrenergic receptor binding in the medial prefrontal cortex and dorsolateral frontal cortex, as well as increases in muscarinic receptor binding in various brain regions. 20 evaluated the effects of asenapine in a validated test battery for manic-like behaviors in Black Swiss mice and found that asenapine exerted antimanic-like effects in some of the behavioral tests performed. 7 compared the long-term effects of asenapine and olanzapine in patients with persistent negative symptoms of schizophrenia and found that asenapine was statistically superior to olanzapine in one extension study. 2 investigated the effects of asenapine on prefrontal N-methyl-D-aspartate receptor-mediated transmission and found that asenapine facilitated NMDA-induced currents in pyramidal cells of the medial prefrontal cortex. 18 systematically reviewed the metabolic risk profile of newer second-generation antipsychotics, including asenapine, iloperidone, lurasidone, and paliperidone. 22 explored the effects of asenapine in bipolar I patients meeting proxy criteria for moderate-to-severe mixed major depressive episodes. 11 explored the effects of asenapine on cognitive and monoamine dysfunction elicited by subchronic phencyclidine administration. 1 evaluated the effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in rats. 5 evaluated the potential differential effects over time of asenapine and olanzapine compared with placebo on the Young Mania Rating Scale in patients with manic or mixed episodes in bipolar I disorder. 6 compared the metabolic side-effects of asenapine and iloperidone with olanzapine. 16 described weight changes and metabolic effects of asenapine compared with placebo and olanzapine in adults. 3 examined the effects of asenapine in animal models of psychosis and cognitive function. 13 investigated the efficacy of asenapine on hostility and agitation in patients with bipolar I disorder. 10 investigated the long-term effects in rat brain of multiple doses of asenapine on representative serotonin receptor subtypes. 12 compared the effects of asenapine and paliperidone to haloperidol on depression, anxiety and analgesy in the forced swimming test, elevated plus maze, and hot plate tests in mice. 21 examined possible effects of asenapine on anxiety-like behaviour of mice. 8 evaluated asenapine's effects on depressive symptoms in patients from two 3-week clinical trials. 4 investigated the effects of adjunctive treatment with asenapine on monoaminergic outflow and glutamatergic neurotransmission in the medial prefrontal cortex of the rat. 14 electrophysiologically characterized the in vivo effects of asenapine at dorsal raphe nucleus and hippocampus serotonin-1A, ventral tegmental area D(2), locus coeruleus 5-HT(2A), and alpha(2)-adrenergic receptors in anesthetized rats. 17 provided preclinical evidence for clinical effects of asenapine in schizophrenia.

Benefits and Risks

Benefit Summary

Asenapine shows potential benefits for the treatment of schizophrenia and bipolar disorder. For example, it has been shown to have antimanic-like effects in animal models, improve negative symptoms in schizophrenia patients, and have antidepressant-like effects. 20 7 8 Moreover, asenapine may have positive effects on cognition, possibly through its interactions with NMDA receptors and alpha-adrenergic receptors. 2 19 Additionally, some research suggests that asenapine may have a lower risk of metabolic side effects compared to other second-generation antipsychotics. 18 6

Risk Summary

While showing promise, asenapine, like other antipsychotics, can have potential risks. These include weight gain and metabolic side effects. Further research is needed to fully understand these risks. 18 6 16

Comparison Across Studies

Commonalities

Across studies, a common thread is asenapine's interactions with a wide range of neurotransmitter receptors, particularly those involved in the regulation of mood, cognition, and behavior. These receptors include dopamine, serotonin, alpha-adrenergic, and NMDA receptors. The studies consistently suggest that asenapine exerts complex and often region-specific effects on these receptors in the brain. 9 19 2 10 Furthermore, the studies suggest that asenapine may have beneficial effects in treating both schizophrenia and bipolar disorder. 9 19 22 20 7 8

Differences

While there are commonalities, differences exist in the findings across the studies. The specific effects of asenapine on various brain regions and receptor subtypes can vary, highlighting the need for further investigation into its mechanism of action. For example, the effect of asenapine on NMDA receptor binding has been reported as both a decrease and no change depending on the study. 9 2 Additionally, there is some variation in findings regarding the potential for metabolic side effects associated with asenapine. 18 6 16

Consistency and Contradictions

The research on asenapine suggests that it is a promising drug for treating schizophrenia and bipolar disorder. However, the specific effects of asenapine can vary based on factors like the brain region, dosage, and research design. There are some inconsistencies regarding its impact on NMDA receptors and the risk of metabolic side effects. More research is needed to clarify these findings.

Considerations for Real-World Application

Asenapine has the potential to be a valuable treatment option for patients with schizophrenia and bipolar disorder. It is essential, however, for healthcare providers to carefully consider the potential benefits and risks of asenapine when making treatment decisions. Open communication with patients regarding potential side effects and the importance of regular monitoring is crucial. 18 6 16

Limitations of Current Research

The research on asenapine is still ongoing, and there are limitations to the current findings. More research is needed to understand the long-term effects of asenapine, its impact on different patient populations, potential interactions with other medications, and the effects on pregnant women and children.

Future Research Directions

Future research should focus on further clarifying the mechanisms of action of asenapine, particularly its effects on different brain regions and receptor subtypes. Studies evaluating long-term safety and efficacy, particularly regarding metabolic risks, are also crucial. Additionally, research exploring the potential of asenapine in combination therapy and its effectiveness in different patient populations is warranted.

Conclusion

Asenapine shows promise as a potential treatment option for schizophrenia and bipolar disorder. However, more research is needed to better understand its complex effects on the brain, its long-term safety, and its impact on various patient populations. Healthcare providers should consider the potential benefits and risks of asenapine when making treatment decisions, and open communication with patients about these factors is essential.

Literature analysis of 22 papers
Positive Content
21
Neutral Content
0
Negative Content
1
Article Type
2
2
1
1
22
2.

Effects of asenapine on prefrontal N-methyl-D-aspartate receptor-mediated transmission: involvement of dopamine D1 receptors.

Author: JardemarkKent, MarcusMonica M, ShahidMohammed, SvenssonTorgny H

Improved bipolar disorder symptoms
Improved schizophrenia symptoms

Asenapine, a novel psychopharmacologic agent, facilitates cortical dopaminergic and NMDA receptor-mediated transmission in rats. It may be beneficial for both positive and negative symptoms in patients with schizophrenia.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Asenapine effects in animal models of psychosis and cognitive function.

Author: MarstonHugh M, YoungJared W, MartinFrederic D C, SerpaKevin A, MooreChristopher L, WongErik H F, GoldLisa, MeltzerLeonard T, AzarMarc R, GeyerMark A, ShahidMohammed

Antipsychotic efficacy
Impaired cognition

Asenapine demonstrated potent antidopaminergic properties, suggesting antipsychotic efficacy. However, asenapine, like risperidone and olanzapine, did not improve cognition in normal rats. Instead, at higher doses, it impaired cognitive performance by disturbing motor function.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Adjunctive treatment with asenapine augments the escitalopram-induced effects on monoaminergic outflow and glutamatergic neurotransmission in the medial prefrontal cortex of the rat.

Author: BjörkholmCarl, FrånbergOlivia, MalmerfeltAnna, MarcusMonica M, Konradsson-GeukenÅsa, SchilströmBjörn, JardemarkKent, SvenssonTorgny H

Antidepressant effect enhancement
Depression treatment

This study discusses the clinical and preclinical evidence supporting the use of atypical antipsychotics as adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs) for treatment-resistant depression.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Asenapine effects on individual Young Mania Rating Scale items in bipolar disorder patients with acute manic or mixed episodes: a pooled analysis.

Author: CazorlaPilar, ZhaoJun, MackleMary, SzegediArmin

Reduced manic symptoms
None

Aasenapine and olanzapine were significantly superior to placebo in reducing manic symptoms in patients with manic or mixed episodes in bipolar I disorder.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

6.

Metabolic side-effects of the novel second-generation antipsychotic drugs asenapine and iloperidone: a comparison with olanzapine.

Author: BoydaHeidi N, ProcyshynRic M, PangCatherine C Y, HawkesErin, WongDaniel, JinChen Helen, HonerWilliam G, BarrAlasdair M

SGA efficacy
Metabolic side effects

Preclinical models were used to evaluate the metabolic side-effects of glucose intolerance and insulin resistance for the novel second-generation antipsychotics (SGAs) asenapine and iloperidone, with olanzapine as a comparator.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Long-term effects of asenapine or olanzapine in patients with persistent negative symptoms of schizophrenia: a pooled analysis.

Author: PotkinSteven G, PhiriPhillip, SzegediArmin, ZhaoJun, AlphsLarry, CazorlaPilar

Schizophrenia treatment

This pooled analysis of two 26-week core studies with 26-week extensions compared asenapine and olanzapine as monotherapies in reducing persistent negative symptoms in schizophrenia. While neither study met the primary endpoint of superiority of asenapine over olanzapine, asenapine was statistically superior to olanzapine in one extension study. This analysis provides insights into the treatment effects of both drugs.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials.

Author: SzegediArmin, ZhaoJun, van WilligenburgArjen, NationsKari R, MackleMary, PanagidesJohn

Reduced depressive symptoms

This study evaluated the effects of asenapine on depressive symptoms in patients with bipolar I disorder. Asenapine demonstrated superiority over placebo for mania in patients experiencing acute current manic or mixed episodes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Asenapine exerts distinctive regional effects on ionotropic glutamate receptor subtypes in rat brain.

Author: TaraziFrank I, ChoiYong Kee, GardnerMatthew, WongErik H F, HenryBrian, ShahidMohammed

Asenapine, a new psychopharmacological agent for schizophrenia and bipolar disorder, has a unique receptor binding profile. This study investigated the effects of chronic asenapine administration on glutamate receptors in rat forebrain regions. Results suggest that asenapine has region-specific and dose-dependent effects on NMDA and AMPA receptors, potentially contributing to its unique psychopharmacological properties.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Asenapine induces differential regional effects on serotonin receptor subtypes.

Author: TaraziF I, Moran-GatesT, WongE H F, HenryB, ShahidM

Treats bipolar disorder
Treats schizophrenia

Asenapine, a new medication for treating schizophrenia and bipolar disorder, increased serotonin 5-HT(1A) binding and decreased 5-HT(2A) binding in rat brain regions.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Asenapine effects on cognitive and monoamine dysfunction elicited by subchronic phencyclidine administration.

Author: ElsworthJohn D, GromanStephanie M, JentschJ David, VallesRodrigo, ShahidMohammed, WongErik, MarstonHugh, RothRobert H

Cognitive improvement

Asenapine, an atypical antipsychotic, showed cognitive and motor improvement in monkeys previously exposed to PCP, a model of schizophrenia. It also normalized dopamine and serotonin turnover in specific brain regions. This suggests that asenapine may have potential benefits for treating cognitive dysfunction in schizophrenia.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Differential regional and dose-related effects of asenapine on dopamine receptor subtypes.

Author: TaraziFrank I, Moran-GatesTaylor, WongErik H F, HenryBrian, ShahidMohammed

Dopamine receptor subtype modulation
Psychopharmacological properties

Asenapine, a novel psychopharmacologic agent, has region-specific and dose-dependent effects on dopamine receptor subtypes in rat forebrain.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Weight change and metabolic effects of asenapine in patients with schizophrenia and bipolar disorder.

Author: KempDavid E, ZhaoJun, CazorlaPilar, LandbloomRonald P, MackleMary, Snow-AdamiLinda, SzegediArmin

Glucose changes
Metabolic adverse events
Weight gain

Asenapine was associated with greater weight gain and glucose changes compared to placebo. While weight gain and triglyceride changes were lower than with olanzapine, glucose changes were similar.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia.

Author: FrånbergOlivia, WikerCharlotte, MarcusMonica M, KonradssonAsa, JardemarkKent, SchilströmBjörn, ShahidMohammed, WongErik H F, SvenssonTorgny H

Low EPS liability
Potent antipsychotic activity
Potential benefit for negative symptoms

This preclinical study suggests that asenapine may exhibit highly potent antipsychotic activity with very low EPS liability. Its ability to increase both dopaminergic and glutamatergic activity in rat mPFC suggests that asenapine may possess an advantageous effect not only on positive symptoms in patients with schizophrenia, but also on negative and cognitive symptoms.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone in the treatment of schizophrenia and bipolar disorder: a systematic review and exploratory meta-analysis.

Author: De HertMarc, YuWeiping, DetrauxJohan, SweersKim, van WinkelRuud, CorrellChristoph U

Improved adverse effect burden
Tolerability benefits
Metabolic dysregulations

This review compares the metabolic risks associated with newer second-generation antipsychotics (SGAs) - asenapine, iloperidone, lurasidone, and paliperidone - to those of older SGAs, such as olanzapine and clozapine. While SGAs offer improved tolerability compared to first-generation antipsychotics (FGAs), they can still cause metabolic problems, particularly in patients without prior exposure to antipsychotics, those with first episodes of illness, and children and adolescents.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

19.

Repeated effects of asenapine on adrenergic and cholinergic muscarinic receptors.

Author: ChoiYong Kee, WongErik H F, HenryBrian, ShahidMohammed, TaraziFrank I

Bipolar Disorder Treatment
Schizophrenia Treatment

Asenapine, an antipsychotic medication, increased binding to adrenergic and cholinergic muscarinic receptors in specific brain regions. These effects may contribute to its efficacy in treating schizophrenia and bipolar disorder.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

21.

Effects of repeated asenapine in a battery of tests for anxiety-like behaviours in mice.

Author: EneHila M, KaraNirit Z, BarakNoa, Reshef Ben-MordechaiTal, EinatHaim

Anxiolytic effects

Asenapine, a new atypical antipsychotic, has a broad pharmacological profile with significant effects on serotonergic receptors, suggesting potential anxiolytic effects. This study investigated the effects of asenapine on anxiety-like behavior in mice.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

22.

Effects of asenapine in bipolar I patients meeting proxy criteria for moderate-to-severe mixed major depressive episodes: a post hoc analysis.

Author: BerkMichael, TillerJohn W G, ZhaoJun, YathamLakshmi N, MalhiGin S, WeillerEmmanuelle

Improved depression

This study found that asenapine may be effective for mixed major depressive episodes in patients with bipolar disorder. Asenapine significantly reduced depression scores compared to placebo or olanzapine in this subgroup analysis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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