Asenapine monotherapy in the acute treatment of both schizophrenia and bipolar I disorder

Pharmacy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, UK.
Neuropsychiatric Disease and Treatment (Impact Factor: 1.74). 10/2009; 5(1):483-90. DOI: 10.2147/NDT.S5742
Source: PubMed


Asenapine is a new atypical antipsychotic agent currently under development for the treatment of schizophrenia and bipolar disorder. It has high affinity for various receptors including antagonism at 5HT(2A), 5HT(2B), 5HT(2C), 5HT(6) and 5HT(7) serotonergic receptor subtypes, alpha(1A), alpha(2A), alpha(2B) and alpha(2C) adrenergic and D(3) and D(4) dopaminergic receptors. As with other atypicals, asenapine exhibits a high 5HT(2A):D(2) affinity ratio. Although similar to clozapine in its multi-target profile, it shows no appreciable affinity for muscarinic receptors. Asenapine has shown efficacy in alleviating both positive and negative symptoms of schizophrenia compared with placebo. Although promising, further studies are required in order to determine whether it has advantages over placebo and other antipsychotics in alleviating cognitive impairment associated with schizophrenia. It has also shown long-term efficacy comparable with olanzapine in bipolar I disorder. Asenapine is generally well tolerated and appears to be metabolically neutral. It has low propensity to cause weight gain and prolactin elevation. There were no concerns in the studies about its effects on the cardiovascular system and QTc prolongation. The incidence of extrapyramidal symptoms with asenapine however has been found to be higher than that with olanzapine. It may be a useful alternative to aripiprazole in schizophrenia and bipolar disorder in patients who are at high risk of metabolic abnormalities.

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    • "Its antipsychotic action is believed to be brought out largely by its high affinity for the 5HT 2A receptor. The lack of affinity for muscarinic receptors and the binding to 5HT 2A receptors which leads to dopamine activity in the prefrontal cortex is claimed to translate into improved response, especially in those with cognitive and negative symptoms of schizophrenia [22]. A PET study demonstrated that asenapine had significant occupancy of the dopamine receptors with a good correlation obtained between plasma levels of asenapine and D 2 receptor occupancy . "
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    ABSTRACT: Background The management of schizophrenia has seen significant strides over the last few decades, due to the increasing availability of a number of antipsychotics. Yet, the diminished efficacy in relation to the negative and cognitive symptoms of schizophrenia, and the disturbing adverse reactions associated with the current antipsychotics, reflect the need for better molecules targeting unexplored pathways. Purpose To review the salient features of the recently approved antipsychotics; namely, iloperidone, asenapine, lurasidone and blonanserin. Methods We discuss the advantages, limitations and place in modern pharmacotherapy of each of these drugs. In addition, we briefly highlight the new targets that are being explored. Results Promising strategies include modulation of the glutamatergic and GABAergic pathways, as well as cholinergic systems. Conclusions Although regulatory bodies have approved only a handful of antipsychotics in recent years, the wide spectrum of targets that are being explored could eventually bring out antipsychotics with improved efficacy and acceptability, as well as the potential to revolutionize psychiatric practice.
    No preview · Article · Apr 2013 · European Journal of Clinical Pharmacology
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    • "A review of clinical trials evaluating the efficacy of asenapine in bipolar disorder has been published in several articles [Bishara and Taylor, 2009; Chwieduk and Scott, 2011; Citrome, 2009; Gonzalez et al. 2011; Henry and Fuller, 2011; McIntyre, 2011; McIntyre and Wong, 2012; Pompili et al. 2011; Samalin et al. 2012; Stoner and Pace, 2012]. "
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    ABSTRACT: Asenapine is a new second-generation antipsychotic approved in September 2010 by the European Medicines Agency for the treatment of bipolar disorder. It demonstrated significant efficacy compared with placebo in acute mania or mixed episodes as monotherapy or adjunctive therapy to mood stabilizers (lithium or valproate). Early improvement was noted at day 2 and was strongly associated with response and remission at week 3. Asenapine also appeared effective in treating acute mania in older patients with bipolar disorder. Post hoc analyses of asenapine showed efficacy in treating depressive symptoms during manic or mixed episodes compared with placebo. The efficacy of asenapine in patients with acute mania appeared to remain constant during maintenance treatment. Asenapine was reasonably well tolerated, especially with regard to metabolic effects. There were minimal signs of glucose elevation or lipid changes and the risk of weight gain appeared limited. The prolactin elevation was smaller than other antipsychotic comparators. Only oral hypoesthesia occurred as a new adverse event compared with other second-generation antipsychotics. Asenapine presents several advantages over other second-generation antipsychotics, such as sublingual formulation, early efficacy and good metabolic tolerability. This tolerability profile confirms the heterogeneity of the second-generation antipsychotic class and supports the view of some authors for the need to re-evaluate the boundaries of this group.
    Full-text · Article · Jan 2013 · Therapeutic Advances in Chronic Disease
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    • "Treatment with risperidone showed moderate changes in body weight (average body weight gain 1.0 kg/month), where ziprasidone seemed to induce only slight body weight changes (0.8 kg/month). Asenapine causes up to 0.9 kg weight gain in the first three weeks of treatment [11] and its FDA Package Insert discusses a 52-week regulatory trial causing negligible weight gain over time, suggesting it may also be less metabolically problematic [12]. Nineteen percent of patients treated with asenapine have weight gain as compared to 31% who were treated with olanzapine [13]. "
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    ABSTRACT: A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment with these agents. There is newer literature looking at the etiology of this weight gain and the potential treatments being used to alleviate this side effect. The authors undertook a comprehensive literature review in order to present epidemiology, etiology, and treatment options of weight gain associated with antipsychotics, mood stabilizers, and antidepressants.
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